Herpes Viral Abortion in Domestic Animals

The I'etetqnmyJournal 1997, 153, 253-268

Review

+

Herpesviral Abortion in Domestic Animals

K. C. SMITH

Centre fi~r Preventive Medicine, Animal Health Trust, P.O. Box 5, Newmarket, &tffolh CB8 7DW, UK

SUMMARY

Abortion or neonatal disease may follow infection with several c~, [3 and y-herpesviruses. The c~-herpesvirus, equid herpesvirus-1 (EHV-1), causes single or epizootic abortions or neonatal deaths in equids, and the closely related virus EHV-4 causes sporadic equine abortions. In cattle, the ~-herpesviruses, bovine herpesvirus-1 (infectious bovine rhinotracheitis virus) and bovine herpesvirus-5 (bovine encephalitis virus), and a y-herpesvirus, bovine herpesvirus-4, have all been implicated as causes of abortion. In pigs, suid herpesvirus-1 (SHV-I: pseudorabies virus), an 0~-herpesvirus, and SHV-2 (porcine cytonaegalovirus), a ~-herpesvirus, each cause abortion or neonatal piglet losses. Caprine herpesvirus-1, canine herpesvirus and feline herpesvirus-1, all ~-laerpesviruses, cause abortions or neonatal deaths in goats, dogs and cats, respectively. This review discusses the pathogenesis, pathology and laboratory diagnosis of these herpesviral abortions and neonatal diseases, with an emphasis on experimental studies of each disease. Alternative reviews covering other aspects of each infection, such as the genetic and antigenic structure of the viruses, host immune responses and approaches to vaccination and disease control are indicated at appropriate points in the text.

KE:YWORDS: Virus; herpesvirus; abortion; neonatal; pathogenesis.

HERPESVIRAL A B O R T I O N IN H O R S E S

E q u i d herpesv i rus 1 Equid herpesvirns-1 (EHV-I: formerly EHV-1

subtype 1, or equine abortion virus) and EHV-4 (formerly EHV-1 subtype 2, or equine rhinopnen- monitis x4rus) are serologically cross-reactive, but show limited DNA homology on restriction endonuclease (RE) digests (Sabine et al., 1981; Studdert et al., 1981; Turtinen et al., 1981). EHV-1 causes acute respiratory disease in foals and year- lings, and is the most important viral cause of equine abortion (for reviews see Allen & Bryans, 1986; Crabb & Studdert, 1995). Some EHV-1 isolates also cause a neurological syndrome in horses (Jackson & Kendrick, 1971; Jackson et al., 1977; Edington et al., 1986), which may precede or accompany abortion epizootics. This syndrome differs from other neurotropic 0t-herpesvirus infections as viral antigen has not been demonstrated in neurones, but in endothelial cells of the

brain and spinal cord, resulting in vascnlitis and local thrombo-ischaemic necrosis. Primary EHV-1 replication occurs in the upper respiratory tract and local lymph nodes (Patel et al., 1982; Kydd et al., 1994a,b) and may be succeeded by a cell- associated viraemia involving a latent or non-pro- ductive infection of T lymphocytes, monocytes or macrophages (Patel et al., 1982; Dutta & Myrup, 1983; Scott et al., 1983; Edington et al., 1986; Edington, 1992; Gibson et al., 1992; Slater et al., 1994a). Latent virus has been detected in lymphoreticular tissues and trigeminal ganglia (Welch et al., 1992; Edington et al., 1994; Slater et al., 1994b).

EHV-1 research has been hampered by incon- sistent experimental reproduction of abortion in equids (Gleeson & Coggins, 1980), and most equine studies have employed highly virulent EHV-1 isolates also able to cause neurological disease (Mumford et al., 1994). Respiratory disease, viraemia and abortion can be induced by intranasal challenge of young Balb/c mice (Awan et aL,

1090-0233/97/()30253-16/$12.00/0 © 1997 Bailli~re Tindall

254 THE VETERINARY JOURNAL. 153, 3

1990, 1991), but basic differences in the anatomy of murine and equine placentae limit extrapol- ation of findings on the abortigenic disease in this model. Early experimental studies in ponies (Prickett, 1970; Jackson el aL, 1977) demonst ra ted vasculitis or perivascular cuffing of deep endo- metrial blood vessels in mares exalnined prior to and after abortion, and it was suggested that abortion occurred due to oedema between trophol)last and endometr ia l epithelia (BD,ans & Prickett, 1970), possibly as a result of an imnaulae reaction between the infected toetus and sensitized maternal lymplaocytes.

An ilnportant breaktlarougla came in 19t)l (Edington et aL, 1991) in an experimental study which demonst ra ted that transplacental spread of EH-V-1 was preceded bv viral replication in endothelial cells of the uterus in a paralysed pregnant pony mare infected by the intranasal route. There was an associated lymphocytic vasculitis, local thrombosis and infarction of the microcotyledons of the pregnant uterus. EI-D/-1 antigen was also demonst ra ted in endothelial cells of the allantochorion and umbilical vein. This work was corrob- orated by Smith et al. (1992, 1993) who infected a series of ponies intranasally with a different EHV-I paresis isolate and detected viral antigen expression in endothelial cells of deep endometr- ill arterioles fi'om 6 days post infection (PI). A novel f inding fi'om these studies was that EHV-I antigen expression was widespread in endometr ia l blood vessels over days 9-13 PI, and the associated severe vasculitis and multifocal thronabo- ischaemic microcotTledonm T necrosis could result in precipitate abort ion of a virologically negative foetus before detectable transplacental infection had occurred (Smith el ak, 1992). Comparable abortions had occurred early in previous EHV-1 challenges and field outbreaks (Gleeson & Coggins, 1983; Carrigan el aL, 1991) but had been assumed to be due to maternal stress or pyrexia (Daels el aL, 1989; Swerczek, 1990), and the incidence and epidemiological significance of such abortions in natural EHV-1 epizootics is not known.

Focal thrombosis and cotyledonary infarction have been demonst ra ted in mares experimental ly infected with EHV-1 and examined over days 14-91 PI, ei ther when carrTing an infected foetus or immediately after abort ion of an infected foetus, with a more limited EHV-1 replication in endometr ia l blood vessels (Smith et aL, 1993). In contrast, endometr ia l thrombi w e r e r a r e i n

infected mares carrying normal foetuses. These data formed the basis of tile hypothesis that the degree of viral vasculitis and tln'ombosis ill tile pregnant uterus following an EFIV-I infection could de termine the outcome of the pregnancy (Smith, 1994), possihly as a resuh of local prostaglandin release in addition to direct leakage of free virus or infected cells into the placental circulation at sites of infarction.

Endothel iotropism has not been demonst ra ted in all abortigenic EH\/-I isolates (Patel el al., 1982), and experimental studies suggest that dilI'- erent EH\:-I isolates vm-v in abortigenic potential (Mumtbrd et aL, 1994). The possibiliD' of an ahernative meclaanism of foetal infection not reliant on vascular compromise cannot therefore be ignored. The role of latently infected, or ' inamunologically privileged', leucocytes in the transfer of EHV-1 across the placenta (BD'ans, 1969, 1980) is uncertain, as is the relative import- ance of prolonged low-level viraemia versus lymphoid or ganglionic latency as sites of viral persistence prior to abortions occurr ing after prolonged incubation periods in mares with high levels of neutralizing antil)ody. Answers to these important questions require sensitive molecular assays such as the in situ polymerase chain reaction (PCR) to visualize cells harbour ing latent viral DNA in the blood, endomet r ium, local lympla nodes and senso D, ganglia.

Up to 95% of EHV-1 abortions occur in the last third of pregnancy, and have rarely been observed under natural condit ions before 4 months (Doll, 1952; Allen & BD,ans, 1986). This increased sus- ceptibility of the late pregnant mare to abortigenic infection is likely to relate tO anatomical and endocr ine changes in the placental barrie," which facilitate cotTledonm T infarction as pregnancy proceeds, a l though EHV-1 infection of uterine blood vessels does occur at low level in mares chal- lenged intranasally with virus as early as three months of gestation (Smith, 1994; Smith et al., 1996). A potential association between EHV-1 infection, early embD,onic death and resorption has not been investigated.

The incubation period for EHV-1 abortion var- ies fi'om 9-121 days (Mumford el aL, 1987), and premonitor T signs of respirator 3, disease in the abort ing mare are tmusual. Following abortion, virus is cleared rapidly from the genital tract, and future breeding capacit T is not impaired unless some uterine damage has occurred due to dysto- cia. The post-aborting mare is not immune to sub-

HERPESVIIL~\t. ABORTION 255

sequent infection, but abortions in successive pregnancies are rare (Doll et al., 1955; Osthmd, 1993). Since the aborted foetus and placenta are a major source of infection for in-contact mares, management practices to nlinimize foetal losses during an abortion epizootic rely on rapid diagnosis and isolation of the aborting mare (Horserace Betting Le W Board, 1994).

EHV-1 infected foetuses aborted in late pregnancy are often fresh and enclosed in the placenta, with death due to suffocation following rapid placental separation. Gross examination D, pically reveals some combination of icterus, mec- oniuna staining of the integument, transudation into the body cavities, splenomegaly, perirenal oedema, puhnonary oedema or haemorrhage and pale miliary loci on the capsule and cut surfaces of the liver. Histological examination shows necrosis in the liver, adrenal gland, thymus, spleen, lung and small intestine (Dimock, 1940; Westerfield & Dimock, 1946; Hong el al., 1993). If infection occurs close to term, the infected foal may be born weak, and usually dies within 7 days dne to interstitial pneumonia and viral damage to the liver, lymphoreticular system and adrenal glands, often complicated by seconda D, bacterial infection (Bryans el aL, 1977; Hartlev & Dixon, 1979). In the rare early gestational EHV-I abortion (Doll el aL, 1955; Prickett, 1970), the foetus is grossly autolysed, indicating prior death in utero, with a diffuse scattering of viral inclusion bodies in the major viscera.

Diagnosis of EHV-I abortion or neonatal disease is achieved by recognition of pathognomonic lesions accompanied by virus isolation (\q) or application of the polymerase chain reaction (PCR) using a pooled sample of foetal hmg, liver, thymus and spleen (.Jones el aL, 1948; Randall el aL, 1953; Ballagi-Pord~ny et aL, 1990; Lawrence el al., 1994; O'Keefe et al., 1994). Imnmnofluoresc- ent (IF) (Smith et al., 1972; Gunn, 1991) or immunoperoxidase (IP) staining of tissue sections (Gimeno el al., 1987;Jonsson el aL, 1989; Whitwell el al., 1992; Schultheiss el al., 1993) are also required in some cases. Immunoperoxidase techniques are of value in examination of autolysed tissues (Whitwell et aL, 1992), and may occasionally serve to demonstrate viral antigen in blood vessels of the allantochorion if the aborted foetus is not available. Neither maternal nor foetal serology are reliable diagnostic aids for EHV-1 abortion (Whitwell et al., 1995a).

In addition to mares, colts, stallions and geld-

ings are also susceptible to EHV-1 paresis (Saxegaard, 1966; Crowhurst et aL, 1981; Meyer et al., 1987; Carman et al., 1993), and may develop scrotal oedema and loss of libido in field cases (Greenwood & Simson, 1980; Carman et al., 1993; McCartan et al., 1995). Recent experimental studies on pony colts and stallions have shown that virus localizes in blood vessels of the testes and epididymides in association with vasculitis and thrombosis on days 8 and 9 after intranasal challenge, and that infectious virus may subsequently be shed venereally (Tearle et al., 1996). The epidemiological implications of these findings for abortions occurring on studs remain to be assessed.

E q u i d herpesvirus-2 There is no evidence that equid herpesvirus-2

(EHV-2), a y-herpesvirus, has abortigenic potential (for re~ew see Agius & Studdert, 1994). Exper- imental infection of a mid-gestational equine foetus i~l utero resulted in normal term delivery, although the foal did show mild rhinitis and conjunctivitis, with nasal shedding of EHV-2 for 65 days (Gleeson & Studdert, 1977).

E qu id helpesvirus-3 Equid herpesvirus-3 (EHV-3) causes the self-lim-

iting venereal infection equine coital exanthema (for review see Blanchard el al., 1992). Vesicular and ulcerative lesions occur on the external geni- talia of mares and stallions, and generally resolve in 10-14 days, often leaving areas of depigmented epithelium. Repeated infections can occur in successive covering seasons, although it is not clear whether these represent periodic reactivations fi'om latency (Burrows & Goodridge, 1984). Im,oh,ement of the teats of a nursing mare resulted in minor lesions on the lips and nostrils of the suckling foal (Crandell & Davis, 1985). There is a single experimental report of inoculation of EHV-3 into the amniotic sac of a mid-ges- rational mare, resuhing in abortion after 11 days (Gleeson et al., 1976), but there is no evidence that the virus is abortigenic in natural infections.

E q u i d herpesvinls 4 Equid herpesvirus-4 (EHV-4) is a major cause of

acute respiratory disease (for review see Crabb & Studdert, 1995), but is only occasionally recovered from aborted equine foetuses (Shimuzu et al., 1959; Studdert & Blackney, 1979; Allen et al., 1983). The infection accounted for less than 1% of equine herpes~dral abortions occurring in Ken-

256 THE \~TERINARY JOURNAL, 153, 3

tucky broodmares between 1983 and 1992 (Ostlund, 1993), but represented up to 16% of such virus abortions diagnosed in England between 1987 and 1993 (Whitwell et al., 1995b). EHV-4 ~4raemias have been observed but are rare (Matsumura et aL, 1992).

Specific pathological findings in EHV-4 versus EHV-I abortion have been summarized (Whitwell et aL, 1995b). Lesions common to abortions caused by both EHV-I and EHV-4 included infection of foetal endothelium. The recent finding of a field EHV-4 isolate capable of replicating in vascular endothelial cells of a conventionally reared 6-week-old Welsh pony foal (Bhmden et al., 1995) suggests that EI-~*-4 abortions may have a uterova- scular basis similar to that described for EHV-I.

HERPESVIRAL A B O R T I O N IN CATTLE

Bov ine he~pesvirus-1 Bovine laerpesvirus-1 (BHV-1) causes repeated

outbreaks of respiratm T disease (infectious bovine rhinotracheitis: IBR) and abortion in cattle, and is also the cause of the venereal infections, infectious pustular vulvovaginitis and infectious balano- posthitis (for reviews see Gibbs & Rweyemamn, 1977; Wentick et aL, 1993). Concurrent outbreaks of respiratm T and genital disease are rare (McKercher & Wada, 1964), suggesting that virus usually remains localized at the site of primary infection, with latency in regional sensm y ganglia (Homan & Easterday, 1983; Ackermann & Wyler, 1984). The virus is commonly isolated fi'om bull semen (for rexqew see Afshar & Eaglesome, 1990), and natural or artificial insemination with such semen can cause endometritis, poor conception rates and shortened oestrous periods (Parsonson & Snowdon, 1975). The risk of disease transmission by emblTo transfer is low (tbr review see Philpott, 1993). It is difficult to differentiate respiratmy and genital isolates by RE subtyping (Kennedy & Miller, 1993), and both can cause foetal death and abortion, with some strain variation in abortigenic potential (Miller el al., 1991). Some highly virulent IBR isolates can also cause endometritis, oophoritis, mastitis, dermatitis and fatal diarrhoea in young calves. BHV-I is occasionally recovered from abortions in pigs and sheep.

BHV-1 abortion is a sequel to respiratory infection and viraemia rather than an extension fi'om the vagina. Viral replication has been demonstrated in monocytes (Nyaga & McKercher, 1980),

although the number of circulating infected cells is considered to be low and the form of the viraemia remains controversial (Yates, 1982). The incubation period between intranasal, intravenous or imramnscular challenge with BHV-1 and abortion is 15-64 days, regardless of the stage of gestation (Gibbs & Rweyemamu, 1977). Virus can be isolated fi'oln tbe placenta as early as day 8 PI in experimental infections and slow cell-to-cell spread of virus within placentomes may account for the variable delay between maternal and foetal infection (Kendrick, 197"8). The route of BHV-1 fl-om the placentome to the foetus is unknown, but as viral lesions occur consistently in the liver, baematogenons spread via the umbilical vein is likely. Foetal death occurs within 24 48 h of the onset ot" ioetal infection, but expulsion is delayed for up to 7 days, and virus titres may decline in the foetus over this period, despite remaining stable or increasing in the placenta (Kendrick & Straub, 1967).

Positive virus isolations fi'om the placenta may occur in the absence of placental lesions (Kendrick el al., 1971), and Molello el al. (1966) have suggested that late placental degeneration of BHV-I abortion is seconda D, to the effects of virus activi D, on the foetus. Their study of experimen- tall}, infected pregnant heifers demonstrated extensive placental oedema and detachment, with abundant debris at the uteroplacental interface. Histological examination of the placenta revealed marked stromal and perivascular oedema, necrosis and sloughing of endothelial cells, and extensive coagulative necrosis of villous and non- villous chorioallantois. Lesions were hard to find in the infected foetus owing to death in ulero and autolysis, and viral lesions were not recognized'in the maternal uterus. It was concluded that tbe foetal infection had resulted in severe visceral damage, gradual cessation of placental circulation and generalized placental degeneration leading to detachment and abortion. Experimental infection of heifers has also indicated a role for BHV-1 in earl}, embD,onic death, with viral antigen in necrotic follicles, corpora lutea and embuonic rem- nants (Miller & Van der Maaten, 1986). Maternal uterine lesions were confined to infection of occasional epithelial cells in the horn containing embD, onic debris, with a mononuclear cell infil- tration of the underlying stroma. When expel'- imentally infected heifers were reactivated by dexamethasone, infectious virus was most commonly recovered from the maternal adrenal

HERPESVllL,\t. ABORTION 257

glands, which contained necrotic BHV-1 lesions, but specific pathological changes were not recognized in reproductive tissues despite virus isolation fi'om the ovaries of one out of six animals tested (Miller and Van der Maaten, 1987).

A 10 year survey of 8995 bovine abortions in the United States of America revealed BHV-1 in 5.41% of cases (Kirkbride, 1992). Major outbreaks of abortion have occurred in American beef herds, with over 60% of cows aborting, although the prevalence of abortion in a region generally declines with a reduction in the naive cattle popu- lation owing to natural exposure or vaccination (Kirkbride, 1990a). In a smaller British study of causes of abortion in dairy cattle, BHV-1 was diagnosed in 19 out of 149 cases (12.75%) (Murray, 1990). Naturally occurring BHV-1 abortions are usually observed at 4--8 months of gestation, ahhough intrafoetal or parenteral inoculations of susceptible heifers prior to 3 months reproduces fk)etal disease experimentally (Chow et aL, 1964). There are no premonitory signs, and there may be so little maternal readiness for birth that traction is required to remove the foetus. Placental reten- tion and co~,ledonary degeneration are common, and the aborted foetal carcase is in an advanced stage of autolysis (Gibbs & Rweyemamu, 1977).

Gross BHV-I foetal lesions are usually obscured by antolysis, but there may be white to tan 1-3 mm diameter foci on the liver and lung, serosanguin- ous perirenal oedema and massive renal cortical necrosis and haemorrhage (Owen et al., 1964; Kendrick, 1973; Kirkbride, 1990a). Histologically, there are foci of necrosis with minimal cellular infiltrate in the liver, adrenal, kidney, intestine, lymph node, lung and spleen. Inchlsion bodies may be recognized in cells of the adrenal cortex adjacent to necrotic loci. A necrotizing placental vasculitis is connnon (Kennedy & Richards, 1964).

Diagnosis of BHV-1 abortion is based on immunostaining of foetal tissues (Reed et al., 1971; Edwards et al., 1988), or in situ hybridization for viral DNA (Ayers et al., 1989). The IP technique using BHV-1 monoclonal antibodies is more sensitive than VI (Smith et al., 1989), which is hindered by autolysis and may only be successful in approximately one-third of cases with histological lesions (Kirkbride, 1990a). Maternal antibody titres are usually low at abortion, but examination of paired sera by ELISA from at least 10 in-contact animals may provide indirect evidence of a herd problem. Although the bovine foetus is immunoc- olnpetent for responding to BHV-1 from 5

months, there is little e~fdence of foetal antibody production, owing to rapid foetal death following virus infection (Kendrick & Osburn, 1973).

Neonatal calves may experience a fatal congeni- tal or early post-natal infection with BHV-1 (Reed et al., 1973; Miller et al., 1978; Higgins & Edwards, 1986). Colostrum-deprived calves are especially at risk, and show clinical signs of pyrexia, excessive salivation, nasal discharge and diarrhoea. Post mortem examination reveals multifocal mucosal necrosis in the nasal cavity, oropharynx, oesoph- agus, forestomachs, abomasum, small and large intestines, and miliary foci of necrosis may also be recognized in the liver, spleen, thymus, Peyers patches and adrenal glands. Inclusion bodies are consistently present at the periphery of necrotic lesions outside the alimentary tract, but may only be demonstrable in the epithelial surfaces of early cases. Confirmation of the diagnosis may be achieved by VI, IF or electron microscopy of affected tissues.

B o v i n e he~pesv i rus -4 The boxfine herpesvirus4 (BHV-4) group com-

prises several antigenically related y-herpesviruses (for reviews see Thiry et al., 1989; Gol~ & Ludwig, 1991). The majority of BHV-4 isolates are only mildly pathogenic or avirulent for cattle, and their role as primary abortigenic pathogens is debat- able. Relatively higher prevalences of BHV-4 antibodies have been recorded in aborting compared with clinically normal animals (Naeem et aL, 1989; Fitton et aL, 1990), and recovery of BHV4 from 47 out of 8995 aborted bovine foetuses is recorded (Kirkbride, 1992), but these data must be bal- anced against the fact that viruses of the BHV4 group are frequently isolated from a varie D, of organs in clinically normal cattle (Thiry et al., 1989). Co-infections with other agents such as bovine diarrhoea virus may occur in aborted calves (Reed et al., 1979). BHV-4 has also been associated with metritis, particularly in the post-parturient period, when the ~firus may be excreted for long periods in uterine exudate (Parks & Kendrick, 1973; Wellemans et al., 1984; Castrucci et al., 1986; Abraham & Zissman, 1989).

BHV-4 viraemia involves circulating mononu- cleat" cells, which may facilitate transplacentai infection (Osorio & Reed, 1983). There is a single report of lesions in an aborted calf (Schiefer, 1974): microscopy revealed alveolar thickening in the lungs, with cytomegalovirus-like inclusions demonstrated by electron microscopy in pneumo-

258 THE \rETERINARY JOURNAL. 153. 3

cytes, bile ducts, myocardium, spleen and renal tubules, but no attempt was made to confirm the diagnosis by virus isolation. Kendrick et al. (1976) inoculated an isolate recovered fi'om a case of metritis into foetuses in ulero at various stages of gestation, and this resulted in the death of two foetuses at 3--4 months of gestation with lesions of lymphoid hyperplasia in the lungs and lymph nodes. The pathogenic potential of different BHV-4 isolates has also been studied in rabbits (Naeem et al., 1990): all strains showed a predilection for the reproductive tract, but the fl'equency of abortion and severity of disease varied. Viral DNA could be detected by DNA hybridization and PCR in the rabbit ovary, uterus, placentome and foetus (Naeem el al., 1991a, b). Caution should however be exercised in extrapolating data fi'om these rabbit studies unless parallel experiments have been done in cattle.

Bovine he~pesvirus-5 Bovine herpesxdrus-5 (B\q-I-5) is antigenically

cross-reactive with BHV-1, but is genetically dis- tinct (tor review see Brake & Studdert, 1985; Stud- dert, 1989). The virus causes sporadic cases of infectious encephalitis in calves and yearling cattle, and has occasionally been isolated fi'om aborted boxqne foetuses.

HERPESVIRAL A B O R T I O N IN PIGS

Su id herpesvirus-1 Suid herpesvirus-1 (pseudorabies virus: PRV)

causes reduced fertility, abortion, stillbirth, foetal resorption and mummification in pigs (for reviews see Basker~flle et al., 1973; Christianson, 1992; Mengeling et aL, 1993). Mortality in nursing and young weaner pigs is high, while the disease in older pigs is generally mild (McNutt, 1943). The virus is unusual among the ~-herpesviruses in hav- ing a wide host range, with high mortality rates in species other than pigs. Molecular and imlnunol- ogical factors contributing to virulence have been reviewed (Mettenleiter, 1991; Chinsakchai & Moli- tor, 1994). In pigs, latency is established in both lymphoid and neural tissues (Sabo & Raicani, 1976; Sabo, 1985; Rziha et aL, 1986).

PRV ~4raemia involves latent infections of the lymphocyte and neutrophil fractions of peripheral blood (Wittmann et aL, 1980), which facilitate haematogenous and lymphatic dissemination of virus to secondary sites such as the pregnant uterus.

Viraemia is not considered to be important in PRV neurological disease, with signs being ascrib- able to ascending spread of virus along peripheral nerves. Spread of PRV between pigs is usually by the respiratory route, although other species may be infected either intranasally or by local inoculation.

Different isolates of PRV may differ in vil-ulence (Baskerville el al., 1973; Iglesias & Harkness, 1988). The latter authors used two clones from a PRV isolate to infect 12 sows at 85 days of gestation, and noted that whereas one clone (Ls-1) produced severe and acute illness, the other (Ls- 2) caused only mild transient or subclinical infection. Some sows infected with Ls-1 produced munanfified virus-negative piglets, but transplacental infection only occurred in one sow infected with Ls-2. Perinatal infection occurred in piglets fi-om both groups. This study confirms that while abortion may occur due to viral infection of toetuses and placentae, reproductive failure can he due to the non-specific effects of severe maternal pyrexia. The latter presentation involves abortion or term deliver)' of mummified foetuses which do not yield infectious virus or contain viral lesions, and maternal anorexia or neurological dysflmc- tion may precede or accompany abortion. This phenomenon has also been reproduced experimentally in gilts by Kluge and Mare (1973), who did not demonstrate viral lesions in aborted foetuses, placentae or maternal uteri, but estimated that the time of intrauterine foetal death of mumnaified toetuses had coincided roughly with the peak of pyrexia in the dam.

Uterine patholo~, associated with establishment of a toetal infection has not been detailed, and it was suggested by Hsu el aL (1980) that foetal death was generally due to severe placental pathology. Nau~3,nck and Pensaert (1992) used surgical inoculation of the uterine artel T with either PRV-infected mononuclear cells or cell-fi'ee virus to demonstrate that only cell-associated PRV was abortigenic by this route in vaccinated sows. These data suggest a critical role for cell-to-cell spread of virus within the porcine endometrium in allowing transplacental infection of piglets despite high levels of neutralizing antibody. The authors further suggested that the likelihood of transplacental PRV spread would be related to the number of circulating virus-infected cells. A corre- lation was noted between the experinaental incubation period for abortion, the pathological and virological findings in the aborted foetuses and

l-I ERPESVI RAL A B O R T I O N 259

the duration of virus excretion in vaginal discharges. Abortions occurring 3 clays PI were associated with grossly normal loetuses presenting small early visceral lesions on inamunofluoresc- ence, and virus was excreted in vaginal discharges for 4-5 da},s after abortion. By contrast, abortions occurring 10-12 days PI showed variable foetal mummification, large foci of necrosis affecting the liver and skin positive by immunofluorescence, and absent or short-lived (24-48 hours) vaginal excretion of virus.

The effects of PRV infection on unborn pigs vary with the stage of gestation. Sows infected in the first third of gestation may resorb or abort the embD'os, and return earl}* to oestrus. D, qaen infection occurs in mid-gestation, most of the litter may die in ulero, and such sows commonly deliver a mixture of live normal piglets and mumnaified foetuses at term (Morrison &Joy, 1985). If infection occurs during the last month, then both weak live piglets and dead foetuses showing variable degrees of autolysis will be delivered.

Characteristic gross and microscopic PRV lesions are produced when foetuses and placentae are infected in late gestation. Pale miliary foci may be recognized grossly on dissection of the liver and spleen. Microscopic lesions of coagulative necrosis are present in liver, spleen, adrenal gland and hmgs, with viral inclusion bodies occasionally evident in surrounding hepatocytes and interstitial cells (Wohlgenmth et aL, 1978). Examin- ation of the loetal brain may reveal non-suppurative meningo-encephalitis. The tissues of munanaified fbetuses seldom have histological lesions. A proportion of placentae show multifocal coagulative necrosis of the chorionic villi, with viral inclusion bodies in the trophoblast and occasionally in naesenchvnaal cells (Hsu el aL, 1980); in less severe cases, extensive searching is required to find trophoblast inclusions. In piglets with disseminated neonatal disease, viral replication has been demonstrated in epithelial surfaces, endothelial cells and local parenchyma, with an organ distribution similar to EHV-1 in aborted foetuses (Corner, 1965).

Laboratory diagnosis of PRV abortion may be assisted by IF, IP and VI (Allan el aL, 1985; Kirk- bride, 1990b). Virus isolation in cell culture or in rabbits is more sensitive than IF, and both tests are more likely to yield positive results where infection has occurred late in gestation without subsequent mummification. The preferred tissues for examination are foetal lung, liver, and spleen for

IF, with the addit ion of kidney and brain in a tissue pool for VI. The mummif ied tissues o f piglets which have died prior to 12 weeks of gestation and been carried to term are se ldom diagnostic, but col lect ion of paired sera from at least 10 in-contact pigs should demonstrate seroconversion in a proport ion of animals in which PRV is circulating.

S u i d he~pesvirus-2 Suid herpesvirus-2 ( S H V - 2 : porcine

cytomegalovirus) is a [3-herpesvirus (for review see Ohlinger, 1989). Infection of pregnant sows results in small litters and a combination of mummified, premature and weak undel-weight or stillborn term fbetuses. Subsequent conception rates and litter sizes may be reduced. Neonatal infection canses valTing degrees of necrotizing non-suppurative rhinitis with cytomegalic inclusions in nasal glands (inclusion body rhinitis) (Done, 1955). Pigs up to 12 weeks old may be affected in naive herds, but high mortality occurs only in animals younger than 4 weeks (Corner et al., 1964). Severe systemic disease in mature pigs is unusual.

Transplacental SHV-2 infection has been reproduced experimentally by intranasal challenge of pregnant sows between 31 and 85 days of gestation and post mortem examination of piglets removed by Caesarean section at term (Edington el aL, 1977). Foetal death occurred 4-6 weeks PI regardless of the stage of gestation, and decom- posing or mummified foetuses were retained in ulero. Autolysis often hampered VI and histopa- tholo~;, but cytomegaly and intranuclear inclusion bodies were noted in the liver and lung of better preserved piglets. SHV-2 was never isolated from placental tissues, and no histological lesions were seen in the placentae of virologically positive foetuses which had recently died.

In natural outbreaks of disease, transplacental infection close to farrowing results in congenitally infected foetuses which usually die within the frst week of life. Post mortem examination reveals pul- monary oedema, congestion or consolidation; hydrothorax; and haemorrhages on the heart, lungs, intestines and kidneys. .Cytomegalic inclusions may be recognized in capillary endothelium, macrophages and renal tubules. Some piglets may show a non-suppurative meningoenca- phalitis.

Studies in young piglets have demonstrated a striking age-related variation in the outcome of SHV-2 infection. Experimental infection of 1-day-

260 THE VETERINARY .|OURNAL, 153, 3

old gnotobiotic piglets resulted in severe disseminated infection, with viral replication in endothelial cells and macrophages leading to haemorrhage and oedema in the hmg, kidney, adrenal and lymph nodes. Less severe and non-fatal cases in piglets infected at 16 days of age showed a more epitheliotropic pattern of viral replication, with infection of nasal glands, renal tubules, salivary glands, seminiferous and epithelium, gastrointesti- nal mucosa and hepatocytes. A number of cases showed infection of both reticulo-endothelial and epithelial cells (Edington et al., 1976).

HERPESVIRAL A B O R T I O N IN GOATS

Caprine heTpesvirus Caprine herpesvirus-1 (CHV-1) causes abortion

and neonatal mortality, vulvovaginitis and balano- posthitis in goats (Hornet, 1987; Merrall, 1987; Thompson, 1987; Tarigan et al., 1990; for review see Koptopoulos, 1992). Abortion can be induced experimentally by the intravenous or intranasal infection of pregnant goats with CHV-1 at 3-4 months of gestation (Berrios et al., 1975; Waldvo- gel et al., 1981). The latter authors were able to recover infectious virus from the placentae of two goats and from the lung of one foetus following experimental CHV-1 abortion, but nonetheless suggested that the abortions had occurred primarily due to maternal disease and pyrexia. Severe disease may occur in neonatal kids, which show clinical signs of pyrexia, conjunctivitis, oculonasal discharge, dyspnoea, abdominal pain and weak- ness leading to death within 1-4 days (Be,'rios et aL, 1975; Brake & Studdert, 1985). Post mortem examination reveals erosive, ulcerative and necrotic mucosal lesions throughout the gastrointesti- nal tract, but especially the large intestine. Local epithelial cells are swollen and vacuolated on microscopy, and may contain intranuclear inclusion bodies. In the caecum and colon, extensive mucosal ulceration may progress to transmu- ral necrosis and oedema, with accompanying sub- mucosal inflammation. Viral replication outside the alimentary tract is very restricted following intranasal administration, but specific lesions can also occur in the brain, adrenal glands, urinary bladder, heart, liver, kidneys, spleen, hmgs, lymph nodes and skeletal muscles of kids infected with CHV-1 by the intravenous route (Waldvogel et al., 1981; Papanastasopoulou, 1991). Diagnosis may be confirmed by VI on bovine turbinate, foetal

lung or caprine choroid plexus cultures, or by immunostaining or electron microscopy of tissue sections.

HERPESVIRAL A B O R T I O N IN D O G S

Canine he~pesvirus Canine herpesvirus (CHV) is associated with

abortion, stillbirth, infertility and neonatal disease in bitches (for review see Anvik, 1991). Self-linfit- ing lesions occur on the penis and prepuce of male dogs and vagina of bitches, and generally involve hyperaemia and lymphoid nodules rather than vesiculation or ulceration (Poste & King, 1971; Hill & Marc 1973; Ladds, 1993). Infection may also cause mild upper respiratory tract disease in puppies over 5 weeks of age and in aduh dogs (Appel et al., 1969; Huxsoll & Hemelt, 1970). Canine herpesvirus viraemia is difficult to detect in bitches, and is entirely leucocyte-associated (Carmichael, 1970). Foetal infection has been produced by intravenous inoculation of bitches with CHV at 47-53 days of gestation, resulting in term delivery of stillborn or congenitally infected puppies (Hashimoto et al., 1982), although the more usual clinical presentation is of neonatal or early post-natal infections acquired either on pass- age through the birth canal at whelping or from oronasal secretions from the bitch or infected lit- termates (Carmichael el at , 1965; Stewart el at , 1965; Carmichael, 1970). Microscopic examination of tissues from stillborn or premature puppies following suspect intra-uterine infection reveals foci of necrosis with intranuclear inclusion bodies in the liver, spleen, kidney and heart. Foe- tal endothelium is commonly involved, and virus can be recovered from many foetuses (Hashimoto et al., 1979). Where placentae are available for examination, multifbcal necrosis may be recognized in the labyrinth, with viral antigen and inclusion bodies in trophoblast epithelium and endothelial cells, and mural degeneration and vasculitis may affect allantoic blood vessels (Hashimoto et al., 1979, 1982). Recent work (Okuda et al., 1993a, b) has demonstrated that natural CHV infection in bitches is succeeded by latency, and that recrudescence and repeated nasal and vaginal shedding may be achieved by prednisoione administration.

Infection of puppies up to 3 weeks of age is facilitated by the sub-adult body temperature and incompletely developed thermoregulatory

HERPESVIRAL ABORTION 261

capacity of the canine neonate, and viral replication and mortality can be reduced by artificial elevation of the body temperature (Carmichael, 1970). Signs of neonatal disease generally appear from 5-14 days of age, and are characterized by anorexia, abdominal pain, diarrhoea, dyspnoea and crying. Some puppies may show opisthotonus and paddling of the limbs (Cornwell & Wright, 1969). Post mortem examination of affected pups characteristically reveals ecchymotic renal haemorrhages, accompanied by splenomegaly and sero- sanguinous effusions into the body cavities, with muhifocal necrosis and haemorrhage in the kidneys, liver, spleen, hmgs and adrenal glands (Cornwell el al., 1966; Yanagisawa et al., 1987; Kojima et aL, 1990). Inclusion bodies are rare, but may be recognized in renal endothelium or in the

adrenal cortex, and viral antigen is also present in reticulo-endothelial cells of lymph nodes and spleen. Infection of the brain resuhs in non-suppurative meningo-encephalitis (Percy et aL, 1968), with spread to the central nervous system being primarily haematogenous, ahhough viral antigen has been demonstrated by IF in nerve trunks and trigeminal ganglia. The virus may be isolated fi'om infected visceral tissues on canine cell monolayers. Mortaliu, approaches 100% in infected litters, and residual granulomatous encephalitis, interstitial pneumonitis, segmental renal necrosis and renal, cerebellar and retinal dysplasia may be present in stuMving puppies (Percy et al., 1971; Albert el al., 1976).

has resulted in abortion, stillbirth or generalized neonatal infection, but abortion is difficult to reproduce by intranasal inoculation (Johnson, 1964; Hoover & Griesemer, 1971a), and Gaskell and Dawson (1994) have suggested that abortions occuring after FHV-1 infection are usually due to severe maternal rhinopneumonitis rather than foetal infection. Isolation of virus from the tissues of foetuses aborting during naturally occurring feline viral rhinotracheitis has not been reported, although virus has been recovered from the uterus, placenta, amniotic fluid and vagina of intravenously infected queens with aborted or stillborn foetuses, and necrotic lesions with viral antigen expression occurred in the uterus, placenta, vagina and foetal liver of these experimental cases (Hoover & Griesemer, 1971a). Congeni- tal infection of kittens has also been induced as a resuh of intravaginal instillation of virus (Bittle & Peckham, 1971). In this study, kittens died due to generalized herpesvirus infection in the first 3 weeks of life, and post mortem examination revealed fibrinosuppurative rhinotracheitis, bron- chopneumonia and muhifocal hepatic necrosis, with viral inclusion bodies in respiratory epithelium and hepatocytes. In young kittens, an unusual predilection of this herpesvirus for grow- ing bone at a variety of sites including the nasal turbinates has been recognized, with necrosis and viral inclusion bodies at sites of osteogenesis (Hoover & Griesemer, 1971b).

HERPESVIRAL ABORTION IN CATS

Feline herpesvirus-1 Feline viral rhinotracheitis is caused by feline

herpesvirus 1 (FHV-1). The respiratory disease is a problem in unvaccinated kittens and cats, particularly in catteries (for reviews see Crandell, 1972; Gaskell, 1988; Dawson & Gaskell, 1993). Most cats recover in 7-14 days, but mortality can be high in kittens and debilitated animals, particularly if immunosuppressed by concurrent infection with feline immtmodeficiency virus or feline leukaemia virus. Since respiratory infection is not usually succeeded by viraemia, subsequent abortion is rare (Kennedy & Miller, 1993). A carrier state is common in cats, and it is likely that latency is established in trigeminal ganglia (Gaskell & Povey, 1979; Gaskell et al., 1985). Intravenous inoculation of specific pathogen-free queens in late gestation

CONCLUSIONS

Most pathogenesis research on the abortigenic herpesviruses has concentrated on horses, cattle and pigs, and has been based upon intensive investigations of the aborted foetus and placenta. Studies of the experimentally infected pregnant uterus and factors affecting transplacental infection and foetal expulsion are less frequent. It will be apparent fi'om this review that the ability of a number of herpesviruses to initiate a leucocyte- associated viraemia is critical to the pathogenesis of abortion, and that abortigenic disease rarely resuhs from spread of infection from the l o w e r genital tract. Research into factors affecting the establishment and maintenance of viraemia in each infection is therefore crucial to an under- standing of herpesviral abortion. As a general rule, those herpesviruses which rarely cause virae-

262 THE VETERINARY JOURNAL, 153, 3

mia, such as FHV-1 in cats and EHV-4 in equids, have a low abor t igenic potential .

Viral infect ion of vascular e n d o t h e l i u m in the uterus, p lacenta and foetus is also a COmlnon and pathogenical ly i m p o r t a n t feature of abor t igenic herpesvirus infections, p resen t ing a rneans for virus to cross the placental barr ier , and result ing in a characteris t ic spec t rum of foetal and placental lesions due to vascular damage , such as vasculitis, o edema , perivascular necrosis, haemor - rhage and effusion into bodv cavities. Variation in the clinical p resen ta t ion of herpesviral abor t ion , such as the t endency for foetal autolysis or m u m - mificat ion in cattle and pigs r a the r than precipitate expuls ion in equids may relate to the increased i m p o r t a n c e of the corpus luteunt over the foe toplacenta l uni t in main ta in ing p regnancy in the f o r m e r group, and need not reflect funda- ntental d i f ferences in the m e c h a n i s m of transplacental infection. T h e spec t rum of herpet ic lesions in the abor t ed foetus or early neona t e is remark- ably consis tent between species, with the liver, kidney, spleen and adrenal glands be ing c o m m o n target sites. Post-natal infect ions due to inhala t ion or ingest ion of infect ious virus, such as BI-B/-1 in calves, SI-W-2 in o lder piglets and capr ine herpesvirus in goat kids, typically assume a m o r e epi- thel iotropic pat tern . Herpes- re la ted abor t ions in which the foetus and p lacenta do not b e c o m e infected, e i ther due to severe mate rna l disease or to d i sp ropor t iona te u ter ine damage , have been recognized in the case of El-IV-l, PRV and FHV-I infections, and may presen t a p r o b l e m in labora- to D, diagnosis. In the case of those infections, such as El-IV-l, for which vaccines fully protect ive against abor t ion are not current ly available, the cont inual i m p r o v e m e n t of labora tory techniques for rapid diagnosis is central to effective disease contro l in o rde r that infected anintals may be p rompt ly isolated fi 'om susceptible in-contacts.

A C K N O W L E D G E M E N T S

T h e author is grateful to Dr ] . A. Mumfbrd and Dr A. S. B lunden for constructive criticisms o f this manuscript . Mrs Sandra Tatum was most helpful in undertak ing literature searches.

REFERENCES

ABRAHAM, A. & Z~SSMAN, A. (1989). Isolation of bovine

herpesvirus-4 from vaginal discharges of cows ill Israel. Israel Journal of Velerinan, Medicine 45, 26---8.

A(:KERMANN, M. & W~a.I-R, R. (19821). The DNA ol'an IPV strain of bovid herpesvirns-1 in sacral ganglia during latency after intravaginal infection. 1.:eterinmy Micro- biolo~, 9, 53-63.

Avsuar, A. & EA(;LV.SO.XU"., M. D. (199(/). Viruses associated with bovine semen, l"eterinan., Bulletin 60, 93-109.

A(;lts, C. T. & STt'DDERT, M.]. (1994). Equine herpesvirus 2 and 5: contparisons with other ntentbers of the subfantily Gammalaerpesvirinae. Advances in VilTts Research 44, 357-79.

AI.t',t-RT, D. M., L~,IAX', M., C..xRXm:,lata., L. E. & Pt-RO,', D. H. (1976). Canine herpes induced retinal dysplasia and associated ocular anomalies. Invesli.galions in Oph- thahnoloKq, 15, 267-8.

AI.IAN, (_;. M., N,h:Nt:t:rv, M. S., Tot)t), D. & M(:Ft.:~R..Xx, J. B. (1985). The rapid detection of At!jeszky's disease virus in pigs by direct imnttntoperoxidase labelling. l "eterinmy Microbiolo©' 10, 481-6.

At H.:y, G. P. & BRW×S, J. T. (1986). Molecular epizooti- olo~', pathogenesis and prophylaxis of equine herpesvirus-I infections. In Proffress in Veterina O' Micro- biolo©' and hnmunolo~', vol. 2, pp. 78-144. Basel: I~lrger.

ALl.t-Y, G. P., Yl~\m;.xx, M. R., Tt'RrlXl.:×, L. W., BRY\XS, J. T. & M(:('ot.Ltxt, W. H. (1983). Molecular epizootiol- ogic studies of equine herpesvirus-1 infections by restriction endonuclease fingerprinting of viral DNA. A met4can.]ou rnal (~" Vetet4nmy Research 44, 263-71.

A.','wk, J. O. (1991). Clinical considerations of canine herpesvirus infection, l'eterina O' Medicine 86, 394-403.

AI'PH., M.J .G . , MI.;NI.;(.;t's, M., P..\l~.soys()y, I. M. & CAI,IM- I(:l H-'.I., L. E. (1969). Pathogenesis of canine herpesvirus in specific-pathogen-fi'ee dogs: 5- to 12-week-old pups. Ameman Journal of I'ete~4nmy l-~t,search 30, 2067-73.

AwAx, A. R., (;IJox(;, ~:'.-C. & Fu-t+D, H..1. (1990). The pathogenesis of equine herpesvirus type 1 in the m o u s e : a i lew m o d e l fo r s t u d y i n g host i e s p o n s e s [o the infection.Journal of General 17rolo~' 71, 1131-40.

AWAY, A. R., Gmsox,J. S. & Fn.:l.t). H.J. (1991). A routine model lor studying EHV-l-iladuced abortion. Research in l.~,letqna~y Science 51, 94-9.

A~I.:Rs, V. K., C()~.Lt×s, J. K., BI_~IR, C. D. & BI-.'¢rY, B. J. (1989). Use of in situ hvbridisation with a biotin}q- ated probe tot the detection of bovine herpesvirus-1 in aborted fetal tissue..Journal of Vetem~my Diaffnoslic Investigation 1,231-6.

BAI.t..X(;I-PoRI~ASY, A., KI.ING[-I~,ORN, B., Ft.I':NSm'R¢;, .1. & BI~E.XK, S. (1990). Equine laerpesvirus type 1: detection of viral DNA sequences in aborted fetuses with the polymerase chain reaction. Veterinmy Micmbiolog 9, 22, 373-81.

BASKI-RVILLI.:, A., M(:F~RR..\N, J. B. & Dow, C. (1973). Aujeszky's disease in pigs. l.~,te~4na O, Bulh, tin 43, 465-80.

B~-RRIOS, P. E., M(:KrR(:Iu-'.R, D. G. & K,x~(.~rr, H. D. (1975). Pathogenicity of a caprine herpesvirus. Ameffcan.]our- hal of Veterinm 7 Research 36, 1763-9.

BrrrLz, J. L. & P~.:(:~uA.x~,J. C. (1971). Comments: genital infections induced by feline rhinotracheitis virus and

HERPESVIRAI. ABORTION 263

effects on newborn kittens. Journal of the Ame~qcan Vet- erina O' Medical Association 158, 927.

Bt..~NCHARI~, T. L., KZNN~:V, R. M. & TtXIONFV, P. L. (1992). Venereal disease. Veterina O, Clinics qf North America (Equine Practice) 8, 191-203.

BI.t'NI)EN, A. S., SMIIII, K. C., BINNS, M. M., ZPIANC;, L., GOWVR, S. M. & MuxlFOmt+, J. A. (1995). Replication of equid herpesvirtts 4 in endothelial cells and synovia f,-om a field case of viral pneumonia and synovitis in a toal../ournal ofComparatiw, Patholo©, 112, 133--40.

BR.~KI.:, F. & STt'ImI.:RT, M.J. (1985). Molecular epidemi- olog3, and pathogenesis of , 'uminant herpesviruses including bovine, buffah) and caprine herpesviruses 1, and bovine encephalitis herpesvirus. Austrafian I/et- erinao,./ou rna162, 331-4.

BR~:~xs, ]. T. (1969). On immunity to disease caused by eqt,ine herpesvirus 1.Journal ~ lhe Amm~can Velerina O' Medical Associalion 155, 294-300.

Bm:~xs,.]. T. (I 980). Herpesviral disease affecting reproduction in the horse. D, lerinarv (2inics of Norlh America (Large Animal Praclice) 2, 303-i 2.

BR',:.xxs, J. T. 8,: I~RICKI.TVI , M. E. (1970). A consideration of the pathogenesis of abortigenic disease caused by equine herpesvirus-1. In Pmceedinff~ of the 2nd lnler- national ConJi,rence on Equine hqectious Diseases, pp. 34-4(I, eds J. T. Bryans & H. Gerber. Basel: S. Karger AG.

BP.',z-\Ns, . l .T., SWERCZEK, T. W., D.\RI.IN(;'ION, R. ~ ' . t~ CR¢m'l.:, M. W. (1977). Neonatal foal disease associated with perinatal infection by equine herpesvirus 1. .]ournal o/Equine Medicine and Surgery 1, 20-6.

Bt'~mows, R. & (;~oDml~¢;t.:, D. (1984). Studies of pe,sistent and latent eqtfid herpesvirus 1 mad herpesvirus 3 infections in the Pirbright pony herd. In Lalenl Her- pesvirus h{fi, clions in l'eterinm~' Medicine, pp. 307-19, eels G. Wittmann, R. M. (.;askell & H.- I. Rziha. Hingham: Ma,'tinus Nijhoff Publications.

C.\rxi.xg, S., N.\(;v, E., CM.mv~tJ., D. & V.~x DR~:t'M~-L, A. A. (1993). Equine herpesvirus type 1 neurological disease and entercolitis in mature s tandardbred horses. .flmrnal of l,>lerina~y Diag'noslic Investigation 5, 261-5.

C uaxm:u.~t.:L, L. E. (1970). Herpesvirus canis: aspects of pathogenesis and immune response. .]ournal of the American D, lerinary Medical Associalion 156, 1714-21.

C~RXlU:~I.U-L, L. E., Sqt'm~:, R. A. & KRoo~, L. (1965). Clinical and pathologic features of a fatal viral disease of newborn pups. American Journal of 1,~terina O' Resean'h 26, 803-14.

CARRIGAN, M., Cos(;Rov~;, P., KIRKI.\ND, P. & SABINE, NI. ( 1991 ). An outbreak of equid herpesvirus abortion in New South Wales. Equine Velerina O, Journal 23, 108-10.

C..~mm'c¢a, G., FRU;ERt, F., CuJJ, V. et al. (1986). A study of herpesvirus isolated f iom clair)' cattle with a history of reproductive disorders. Comparative hnmunolow, Microbiolo~' and h{fectious Diseases 9, 13-21.

C~.×s.\~¢:~,..u, S. & MOIJTOR, T. W. (1994). hnmunobiol - ogy of pseudorabies virus infection ill swine. Veterin- ary hn mu nolo©, and hn mu nopharmacologv 43, 107-16.

C~ow, T. L., MoLvLt.o,J. A. & OWV.N, N. V. (1964). Abor- tion experimentally induced in cattle by the infectious bovine rhinotracheitis virus. Journal of the Amer- ican Veterinary Medical Association 144, 1005-7.

CHRISTIANSON, '~T. T. (1992). Stillbirths, mummies, abortions mad early embryonic death. Veterinary Clinics of North America (Food Animal Practice) 8, 623-3"9.

CORNE~, A. H. (1965). Pathology of experimental Aujeszky's disease in piglets. Research in Veterinary Sci- ence 6, 337-343.

CORNI:R, A. H., Mfr(:llFJJ., D., Jvt.i..vx, R.J. & Mr..kDS, E. B. (1964). A generalised disease in piglets associated with the presence of cytomegalic inchtsions. Journal of Comparative PatholoD, 84, 192-9.

C(m.','wE:lJ., H. J. c . & Wm(;HT, N. G. (1969). Neonatal canine herpesvirus infection: a review of present knowledge, l/ete~qnan' Research 74, 2-6.

CoRYm.:Ll., H . J . C . , WKu.,rr, N. G., C..V~U'BELL, R. S. F. & ROBER'rS, R.J. (1966). Neonatal disease in the clog associated with a herpeslike virus. Veterinary Record 79, 661-2.

Cr~um, B. S. & S'rt'DDVRT, M.J. (1995). Equine herpesvirus 4 (equine rhinopneumoni t is virus) and 1 (equine abortion virus). Advances in Vines Research 45, 153-190.

C~.\XDVLL, R. A. (1972). Feline viral rhinotracheitis (FVR). Adz,anc~ in l'eterinary Science and Comparative Medicine 17, 201.

C~..VXI~ELL, R. S. & D.wls, E. R. (1985). Isolation of equine coital exanthenaa virus (equine herpesvirus 3) fi-om the nostril of a foal. Journal of the American Veter- inary Medical Association 187, 503-4.

CROWEit'RSI, F. A., DU:KI.','soX, (;. & Bt'RROVCS, R. (1981). An outbreak of paresis in mares and geldings associated with equid herpesvirus-l. 1'ete14na O' Record 109, 527-8.

D.u.:t.s, P. F., Sf.u~l~xH-Llrf, G. H., KJxD..u,., H. & Ht~au-s,.]. P. (1989). Prostaglandin release and lt, teolysis associated with physiological and pathological conditions of the reproductive tract of the mare: a review. 1-quine l >lerinao, Journal, Supplement 8, 29-34.

DAwsox, S. g: G.\SKEt.I., R. M. (1993). Problems with respirator y virus vaccination in cats. Compendium on Con- tinuing Education for the Practidng Veterinarian 15, 1347-54.

Dt.~tocK, W, W. (1994). The diagnosis of virus abortion in mares. Journal of the American l'etenna O' Medical Association 96, 665-6.

DoLt., E. R. (1952). Seasonal incidence and fetal age in equine virus abortion. Cornell Veterinarian 42, 505-9.

DoI.I,, E. R., CRow~:, IVl. E. W., BRY.~.NS, J. T. & McCol.i.uM, W. H. (1955). Infection immunity in equine virus abortion. Corndl Veterinarian 55, 387-410.

D()x~:, J. T. (1955). kaa inclt,sion body rhinitis of pigs. Veterinary Record 67, 525-7.

DtTr..~, S. K., & M~m'P, A. C. (1983). Infected centre assay for intracelhflar virus and infective virtts titre of equine lymphocytes infected in vivo and in vitro with equine herpesviruses. Canadian Journal,of Comparative MMicine 47, 64-9.

Emx¢,TOX, N. (1992). Latency of equine herpeswiruses. In Proceedings of the Sixth International Conference on Equine Infectious Diseases, pp. 195-200, eds. W. Plowright, P. D. Rossdale & J. F. Wade. Newmarket: R&W Publications.

EDIN(;TON, N., PI.OWRIGHT, W. & WATr, R. G. (1976). Gen- eralised porcine cytomegalic inclusion disease: Distri-

264 THE \q:.TERINARY JOURNAL. 153, 3

bution of cytomegalic cells and virus..pmrnal of Cam- parative Patholo©' 86, 191-202.

EL)INGI'ON, N., BRII)(;I".S, C. G. & P..VIH., J. R. (1986). Endo- thelial cell ilafection and throntbosis in paralysis caused by equid herpesvirus-l: equine stroke. Archive~ of lqrolo~' 90, 111-24.

El~tNt.rox, N., SmTH, B. & Gmvvmls, L. (1991). The role of endothelial cell infection in the endometriunt, placenta and fetus in equid herpesvirus-1 abortions. Jou r, al of ('omparative Patholo~' 104, 379-87.

EI)INGI'ON, N., W:\vr, R. G., PI.OWRIGIIT, ~'. , WRATHAI_I., A. E. & Doxl.:,J. T. (1977). Experimental transplacental transntission of porcine cytomegalovirus. Cambridge

Jour,al of tIyKiene 78, 243-51. Et~m(;rox, N., Wvt.(:., H. M. & GrlFFmlS, L. (1994). The

prevalence of latent equid Imrpesvirus in the tissues of 4(1 abattoir horses. Equi,e I'eteH,a+ 3' .]our, al 26, 140-2.

El:x..\rl~s, S., \'VIIIrE H., NewxJ.xx, R. H. & N~x~x, P. (19881. A vete,-inarv smwice scheme for the ,apid diagnosis of viral infections in ruminants, using immunofluorescence. Slate l'eled,a O' .]our, al 120, 41-7.

FrlToX, J., Bt-:FNI.IAM,J. & EIm'ARDS, S. (1990). Bovid herpesvirus-4 antibody in cattle in Great Britain (letter). I'eleHna O, RecoM 126, 173.

G.\sm:Lt., R. M. (1988). Herpesvirus of cats. In l'irus l)is- eases i , Laborato O' a ,d Captive ,4 ,imals, pp. 219-32, ed. G. Darai. Massachusetts: Martinus N!ihoff.

G..\sm:t.t., R. M. & Pow:v, R. C. (19791. Feline viral rhinotracheitis: sites of virus replication and persistence in acutely and persistently infected cats. Research i , 15,ler- i ,a U Science 27, 167-74.

G..\s~a-l.t., R. M. & D..\wsox, S. (1994). \:iral-induced upper respirato~ T tract disease. In Igeline Mediciae and Therapeutics, Second Edition, pp. 453-72, eds E. A. Chandler. C. J. Gaskell & R. M. Gaskell. Oxford: Blackwell Scientific Publications.

GASKEI.I., R. M., DENNIS, P. E., Gol)II..\RI), L. E., C()CKI-R, F. M. & W..t.s, J. M. (1985). Isolation of felid herpesvirus 1 fi'om tim trigeminal ganglia of latently infected cats. Journal of General l'/ro/g©' 66, 391.

Gm~s, E. P.J. & RwE~:xu\.m, M. M. (19771. Bovine herpesviruses. Part 1. Bovine herpesvirus 1. l5,terinan' Bulletin 47, 317-43.

(_;msox, J. s., Sl_.vrv:r, J. D.. Aw.\x, A. R. & F.-t.,), H . J . (1992). Pathogenesis of equine herpesvirus-1 in specific pathogen-free foals: primm y and secondary infections and reactivation. Archiw;s of Virolo©' 123", 351-66.

GIMI"NO, E.J., Nt)sl--Tro, E. O., ~¢L\RTIN, A. A., GAI.OSl, C. M., ANOO, Y. & ETCIIEVERRIt;ARA'C M. E. (1987). Demon- stration of eqtfine herpesvirus 1 (EHV-1) in histological sections and tissue cultures by the peroxidase- antiperoxidase (PAP) technique..fimr, al of l'>terina U MMicine 68, 740-2.

G~.v~-so:,:, L. J. & SrUDD~:~Rt, M.J . (1977). Equine herpesviruses. Experi,nental infection of a fetus with type 2. A uslmlian l:ete~inmyJourna153, 360-2.

GI,I:.I-SON, L.J . & Co(\;INS, L. (1980). Response of pregnant mares to equine herpesvirus 1 (EHV-1). (;or, ell Vele~q,m4an 70, 391-400.

G~,e~.:son, L.J., SttH,wax, N. D. & Srt'Di~r:r-r, M.J. (1976).

Equine herpesviruses. Type 3 as an abortigenic agent. Aastralia, l'eterina~y.]ourna152, 349-52.

GoH'z, M. & Lt'mvu;, H. (1991). Biological and molecular aspects of bovine herpesvirus 4 (BHV-4). Compare- live lmmu,olow, Microbiolo, O' and lt!fi, ctious Diseases 14, 187-95.

GREENWOOI), R. E. S. 8~ SIMSON, A. R. B. (1980). Clinical report of a paralytic syndrome affecting stallions, mares and foals on a Tlmroughbred studfarnt. Equi,e 1 "eteri,my.]our, al 12, 113-7.

Gtxx, H. M. ( 1991 ). A direct tluorescent antibody technique to diagnose abortion caused by equine herpesvirus, h'ish Veteri,ao, Journa144, 37-40.

HARH.I.:Y. Vf.J. & DIXON, R.J. (1979). An outl)reak of foal perinatal mortality due to equid herpesvirus type 1: pathological observations. Equiae l'eteriam~, .]our, al 11,215-8.

H..~slllXUrlo, A., HIR..\I, K., ()~.XD.\, K. & Ft31Mor(), '~: (1979). Patholo~, of the placenta and newborn pups with suspected intrauterine infection of canine herpesvirus. America, Jom~ml of l>terinmy Research 40, 1236-4O.

H:\sitlXU>lo, A., Hl~.,d K., Y\xt.u;t'<:ltL T. & Ftiltr, tOl~, Y. (1982). Experintental transplacental inl'ectitm ol pregnant dogs with cani,te herpesvirus. America,.]o,~- hal of l >levi,my Research 43, 844-50.

HR;t;IXS, R. ,]. & EI)W.\RDS, S. (1986). Systemic neonatal bovine infectious rhinotracheitis inlection in suckler calves. 15,teri,am' RecoM 119, 177-8.

HtH., H. & M.\m::, C.J . (1973). Genital disease in dogs caused by can ine herpesvirus. ,4 merican Jou r, al ¢!/ 15'l- er/,a 0' R~;search 35, 669-72.

HoxLxx, E..1- & E.\sH.:r,.w, B. C. (1983). Experimental latent aud ,ecrudescent bovine herpesvirus-1 infections in calves. America,,/ournal of l'eterinmy Research 44, 309-13.

H~)xc;, C. B., DONAIIt'I.:,J. M., Oil.l-S, R. C. el aL (1993). Equine abortion and stillbirth during 1988 and 1989 R)aling seasons..]ouraal of 15,leri,m 7 l)iag',oslic lnvesti- gatio, 5, 560-6.

Hc~ovl-a, E. A. & (;R..:sl-xn-a, R. A. ( 1971 a). Experimental feline I'mrpesvirus infection in the p ,egnant cat. America,Journal of lJalholokq" 65, 173.

Hoovl-r, E. A. & Gml.:sl-xu-r, R. A. (1971b). Bone lesions produced by feline he,pesvi,-us. Laboratory Investi- gation 25, 457.

Horxvr, G. W. (1987). Herpesvirus vulvovaginitis in goats. Ill Proceedings from Goat Seminar 198Z Fou,t- dation for Continuing Education of the New Zealand Veterina, T Association, pp. 73-7. New Zealand: Pal- merston North.

Horsr:z-ua.: BevHx{; I.l.:\'v B~am) (1994). The United King- dom and I,eland Code of Practice on Equid Her- pesvirus 1 (EHV-1) infection. In HBLB ('ommon Codes of Practice fi~r the 1995 Breeding Seasoa, pp. 34-7, ed. P. D. Rossdale. London: HBLB Publicatiolls.

Hst, F. S., Cm', R. M., LEg., R. C. T. & Cllt', S. H. J. (19801. Placental lesions caused by pseudorabies virus in pregnant sows. Journal of the American 15,terinmy Medical Associalion 177, 636--41.

Ht'xsota., D. L. & Hl-ml.l':vr, I. E. (1970). Clinical obse,-va- tions of canine herpesvirus..]ournal of the American Vet- elqna U Medical Association 156, 1706-13.

lc;t.t-sL.\s,.]. G. & Har~xl-ss, J, W. (1988). Studies of trans-

HERPESVI RAL ABORTION 265

placental and perinatal infection with two clones of a single Aujeszky's disease (pseudorabies) virus isolate. Veterinmy Microbiolo.©, 16, 243-54.

.]..U:KSO~, T. A. & K~:YDRU:g., J. W. (1971). Paralysis of horses associated with equine herpesvirus-1 infection. .Journal qf the American Vt, lerina~y Medical Association 158, 1351-7.

.lu:Ks~×, T. A., OsBtR.~, B. I., CORDV, D. R. & KJ-~DR~c~,.J. W. (1977). Equine herpesvirus-1 infection of horses: studies on the experimentally-induced neurological disease, flmrnal of the American Veterinary Medical Assodation 38, 709-19.

JoHsox, R. T. (1964). The pathogen esis of herpes virus encephalitis. II. A cellula," basis for the development of resistance with age. Journal qfExperimental Medicine 120, 359-74.

.]~m~:s, T. C., (;LHS~-R, C. A., MAt'RER, F. D., HA~.~, M. W. & R~mv, T. O. (1948). Transmission and immmunis- ation of equine influenza. A merican./ottrnal tff l~lerilt- my Research 9, 24q-53.

.l~,xssox, L., Bl~c~-Fm~s,.]., RI~:NSTROM, L. H. M,, NI~KtI_-\, T., T~ll<l~o, P. & St'x~2t'ls-r, B. (1989). Equine herpesvirus l (EHV-I) in liver, spleen mad lung as demonstrated hy immtmohistolog), and electron microscopy. Acta |'eterinaria Scandinavica 30, 14 i-6.

Kr:xt)m(:K,.J.W. (1973). Effects of the infectious bo~4ne rhinotracheitis virus on the fetus. Journal r( the A merican l'ete~4nan' Medical Association 163, 852-4.

KZX~RU:K, J. W. & STR~Xt'I~, O. C. (19157). Infections bovine rhinotracheitis-inlZ~ctious pustular x~ulvovaginitis virus. American .Journal of l'elerinmy Research 28, 1269-82.

KI,:XD~U:K,J. W. & Osm'Rx, B. I. (1973). hnmunisation of the hovine fetns with an inactivated infections hovine rhinotracheitis-infectious pustular vulvovaginitis virus. American flmrnal of l),lm4nmy Research 34, 1567-71.

K~.:xl)mcK, J. W., Sc~mVmVR, L. & Srmul~, O. C. (1971). Placental reaction to the infections bovine rhinotracheitis-i,ffectious pustnlar vulvovaginitis virus. Amer- ican Journal of l'eterinaty Research 32, 1045-51.

KENDRICK, J. rt,~Z., OSIWRN, B. I. & KRONI,t'ND, N. (1976). Pathogenicity studies on a bovine herpesvirus. 7"he~% ogenology 6, 447-62.

Ka.:xxvDv, P. C. & MU.LER, R. B. (1993). The female genital system. In Patholo©, of Domestic Animals, pp. 349-469, eds K. V. F. Jubb, P. C. Kennedy & N. Pahner, 4th Edition. San Diego: Academic Press.

KENY~:m', P. C. & l~c~Am~S, W. P. C. (1964). The pathology of abortion caused by the virus of infectious bovine rhinotracheitis. VeteHna O, Patholo~, 1, 7-17.

tORK~mot-, C. A. (1990a). Infectious bovine rhinotracheitis (bovine herpesvirus group 1) viral abortion. In Laboratmy Diagnosis of Livestoch Abortion, pp. 91-7, ed. C. A. Kirkbride, 3rd Edition. Antes: lowa State Uni- versity Press.

tO~RIt~E, C. A. (1990b). Porcine abortion and stillbirth caused by porcine herpesvirus (Aujeszky's or pseudorabies virus). In Laboralo~ Diagnosis of Livestoch Abor- lion, pp. 98-110, ed. C. A. Kirkbride, 3rd edition. Ames: Iowa State University Press.

ICmK~rUI~E, C. A. (1992). Viral agents and associated lesions detected in a 10-year study of bovine abor-

tions and stillbirths. Journal of VeteHnmy Diag~wstic Investigation 4, 374-9.

Ki.t,~:r, J. P. & Mare:-, C.J . (1973). Swine pseudorabies: Abortion, clinical disease, and lesions in pregnant gilts infected with pseudorabies virus (Aujeszky's disease). Anu, Hcan .Journal of Veterinmy Research 35, 91 I-5.

KQIIMA, A., Ft'II,~AMJ, F., TAKESmTa, M. et al. (1990). Out- break of neonatal canine herpesvirus infection in a specific pathogen-free Beagle colony. Japanese Journal of l/ete~nmy Science 52, 145-54.

KopxoPoCLoVs, G. (1992). Goat herpesvirus I infection: a rex4ew, l/ele14nal) , Bullelin 62, 77-84.

K~v,, J. H., S~wrH, K. C., HA~x'.-xx-r, D., Llvzsa~; G.J . & Mt.~woaD, J. A. (1994a). Distribution of equid herpesvirus-1 in the respiratory tract of ponies: implications 1or vaccination strategies. Equine $~tel~naty .]om~m126, 466--9.

m~l), J. H., S~lrrll, K. C., HA~'N..XNT, D., LIX~SA~,, G.J . & Mt'xwoRtt, J. A. (1994b). Distribution of equid herpesvirus 1 in the respirator), tract-associated lymphoid tissue: implications for cellular immunity. Equine 1.'ete~inmyJouma126, 470-3.

LADOS, P. W. (1993). The male genital system. In Pathol- o©, of Dome.~ticAnimals, pp. 471-529, eds K. V. F.Jubb, P. C. Kennedy & N. Palmer, 4th Edition, San Diego: Academic Press.

LAWREN(:F, G. L., GII.KERSON, J., LO\T., D. N., SAnlXE, M. & WH.-U.CrW, .1" M. (1994). Rapid, single-step differentiation of equid herpesvirus 1 and 4 from clinical material using the polymerase chain reaction and virus-specific primers. Journal of Virolo~cal Methods 47, 59-72.

M.vrst'Mt'~.~, T., St,¢;n,z.x, T., IMA(;AWA, H., Ft'Kt'XA¢;A, Y. & Ka,~lal).X, M. (1992). Epizootiological aspects of ~ e 1 and t),]~e 4 equine herpesvirus infections among horse populations. Journal of Vetelinar), Medical Sdolce 54, 207-11.

McCARTAN, C. G., WOOD, J. L. N., Mt'MFORD, J. A. & Rt,s- sH.t., M. M. (1995). Clinical, virological and serological description of equine herpesvirus-1 paresis and neonatal foal disease on a stud farm. Veterinary Record 135, 7-12.

McKERcm:R, D. G. & WADA, E. M. (1964). The virus of infections bovine rhinotracheitis as a cause of abortion in cattle. Journal of the American Vetelinary Medical Association 144, 136--42.

McNtTr, S. H. (1943). Some infectious diseases involving the nervous system of swine. North Amelican Veter- inmian 24, 409-17.

ME~t;m~c, W. L., PAvc, P. S. & LAC,~:R, K. M. (1993). Virus-induced maternal reproductive failure in swine. Journal of the Ame~Tcan Vetetqnar), Medical Association 203, 1268-72.

MER~.L, M. (1987). The aborting goat. In Proceedings of a Course in Goat Husbandr), and Medicine, pp. 181-98, New Zealand Veterinary Association Foundation for Continuing Education Publication No. 106. New Zea- land: Palmerston North.

METI'ENLF_ITER, T. C. (1991). Molecular biology of pseudorabies (Aujeszky's disease) virus. Comparative lmmunolo~,, Micmbiolo~ and Infectious Diseases 14, 151-163.

266 THE VETERINARY JOURNAL, 153, 3

ME~ER, H., THEIN, P. & HUBERT, P. (1987). Characteris- ation of two equine herpesvirus (EHV) isolates associated with neurological disorders in horses. Jour- nal of Veterina D, Medidne B34, 545-8.

MILLER, J. N. & VAN DER MAATEN, M..1. (1986). Expel-- imentally induced bovine rhinou'acheitis virus infection during earl)' pregnancy: Effect on the bovine corpus luteum and conceptus. American Journal of Vet- erina D, Research 47, 22.'3---8.

MII,LER, J. M. 8+2 VAN DER M+&-kTEN, M. J. (1987). Early embD,onic death in heifers after inoculation with bovine herpesvirus-1 and reactivation of latent virus in reproductive tissues. American .]ournal of VeteHna O, Research. 48, 1555-8.

MII.I.ER, J. M., WHETSTONE, C. A. & v..xx DER I~I.-L-VFI.~N, M.J. (1991 ). Abortifacien t potential of bovine herpesvirus type 1 isolates that represent three suhtypes deter- mined by restriction endonuclease analysis of viral DNA. American Journal of Vete~ina U l~eseardt 52, 458-61.

MU.LER, R. B., SMmt, M. W. & L.xwsox, K. F. (1978). Some lesions observed in calves born to cows exposed to the virus of infectious bovine rhinotracheitis in the last trimester of gestation. Canadian Jour- hal of Comparative Medicine 42, 438-45.

MOLEI.I.O, .l. A,, CHow, T. L., Ox~a-x, N. & J~:xst:x, R. (1966). Placental pathology V. Placental lesions of cattle experimentally infected with infectious bovine rhinotracheitis virus. American .Journal of VeteHna O' Research 27, 907-15.

Mo~msox, R. B. &Joy, H. S. (1985). Prenatal and pre- weaning deaths caused by pseudorabies virus and porcine parvovirus in a swine laerd..]ournal of the Amtn{can Vete~qnm), Medical Association 187, 481-3.

MUMFORD, J. A., ROSSDALE, P. D., JESSE'I-r, D. M., G..xxx, S. .J., Ot'sEv, J. & CooK, R. F. (1987). Serological and Vil'- ological investigations of an equid herpesvirus 1 (EHV-1) abortion storm on a stud farm ill 1985../ou~= hal of Reproduction and Fertility Suppl. 35, 509-18.

Mt~lmRr), J. A., HANNANq', O., JESSETr, D. M., O'NEu.L, T., SMITH, K. C, 8c OSTLUND, E. N. (1994). Abortigenic and neurological disease caused by equid herpesvirus-1. In Proceedings of the 7th International Conference on l'quine Infectious Diseases, pp. 261-275, eds W. Plowright & H. Nakajima. Newmarket: R&W Pub- lications

MvRm.W, R. D. (1990). A field investigation of causes of abortion in dairy cattle. VeteHna+y Record 127, 543-7.

NAEEM, K., Gm:.xL, S. M. & WERDIN, S. E. (1989). Preva- lence of bovid herpesvirus-4 and its antibody in cattle in Minnesota. Ame,{can Journal of 1~ete~qnmy Research 50, 1931-5.

NAEEM, K., CA'tWOOD, D. D., WERm~, R. E. & Gm:~L S. M. (1990). Evaluation of pregnant rabbits as a laborato~ T model for bovid herpesvirus4 infection. American

Jour?~al of VeteHnat 3, Research 51,640-4. NAEEM, K., CAX~,VOOD, D. D., Go~,sXl., S. M., WERDIN, R. E. 8c

NAEEIVl, K., ML'RTAUGH, M. P. 8¢ GoY.xl., S. M. (199113). Tissue disu-ibution of bovid herpesvirus-4 in inoculated rabbits and its detection by DNA hybridisation and polymerase chain reaction. Archives of Virologl, 119, 239-55.

MURTAUt:;H, M. P. (1991a). Variation in the pathogenic

potential and molectdar characteristics of bovid herpesvirus-4 isolates. Vetenna U Microbiolog 3, 27, 1-18.

N..xt,~3XCK, H. J. & PI:+NS..XER'r, M. B. (1992). Abortion induced by cell-associated pseudorabies virus in vaccinated sows. American Journal of Veterina U Research 53, 489-93.

N~:.~(zA, P. N. & McKERolER, D. G. (1980). Pathogenesis of bovine laerpesvirus-1 (BHV-1) infections: inter- actions of the virus with peripheral bovine blood celhdar components. Comparative Immunolo&r~,, Micro- biolo~, and Infectious Diseases 2, 587-602.

O'KEEv,:., J. S., JuLia,x, A., MORIARTY, K., MURRAY, A. & Wu.~.s, C. R. (1994). A comparison of the polymerase chain reaction with standard lahoratou, methods for the detection of EHV-1 and EI-D/-4 in archival tissue samples. New Zealand I,'eterinasyJourna142, 93-6.

Om.ly(;t-k, V. (1989). Porcine cytomegalovirus. In Her- pesvirus Diseases of Cattle, flm:ws and Pigs, pp. 3215-333, ed. G. Wittmann. Boston: Kluwer Academic Pnblishers.

O~;tq~A, Y., HAsl..xurro, A., Yaxt.-\(;t'cJtl, T, et al. (1993a). Repeated canine herpesvirns (CHV) reactivation in clogs by an immunosuppressive drug. Cornell Veterin- arian 83, 291-302.

OKt'l~A, Y., IsI.D..~, K., H..xsltmoao, A. et aL (199313). Virus reactivation in bitches with a medical history of herpesvirus infection. Ame14can Journal of l'eterinarr Research 54, 551-4.

Osomo, F. A. & RH.:D, D. E. (1983). Experimental inoculation of cattle with bovine herpesvirns-4: evidence fi)ra lymphoid-associated persistent infection. Amer- ica n.]ou rn a I r~f Velerin a ~3' Re~vrd 44, 975-80.

OSFI.tNI), E. N. (1993). The equine herpesviruses. Veter- inal 3, ('linics of North America (Equine Practice) 9, 283-94.

Owvx, N. W., CEu)w, T. L. & Mot+:Lt.o, J. A. (1964). Bov- ine fetal lesions experimentally produced by infections hovine rhinotracheitis virus. American Journal of VeteHna U Rewarch 25, 1617-25.

PAPANASTASOPOt'I.Ot', M., KOPTOPOt'I.OS, G., LEKK..\S., PAPA- I)oPotLos, O. & Lt'mvu;, H. (1991). An experimental study on the pathogeniciu, of the caprine herpesvirus t)qge 1 (Cl~Z-1). Comparative ImmunoloD,, Microbiolo~' and hTfectious Diseases 14, 47-53.

P.~RU.s,J. B. & l~-yDmc~,J. W. (91973). The isolation and partial characterisation of a herpesvirus fi-om a case of bovine metritis. Archiv fiir die Gesamte Wirll.~forsdllltlg 41 ,211 -5 .

PARSO.~SON, I. M. & Syowt~ox, W. A. (1975). The effect of natural and artificial hreeding using bulls infected ~dth, or semen contaminated with, infectious bovine rhinotracheitis virus. Australian VeteHnat 3, Journal 51, 365-9.

PATt-L, J. R., E01x(.roy, N. & MuxlvORD, J. A. (1982). Vari- ation in cellular tropism between isolates of equine herpesvirus-1 in foals. Archives of Virology 74, 41-51.

PERCY, D. H., OI..~Xt)ER, H.J. & C,.~R~UC~tAEL, L. E. (1968). Encephalitis in the newborn pup due to a canine herpesvirns. Veterina U Patholo D, 5, 135--45.

PERCY, D. H., CARMICHAEI., L. E., ALBER'F, D. M., KIN(;, J. M. &Joyas, A. M. (1971). Lesions in puppies surviv- ing infection with canine herpesvirus. VeteHnmy Path- oloKv 8, 37-53.

PHH.mrr, M. (1993). The dangers of disease trans-

HERPESVIRAL ABORTION 267

mission by artificial insemination and embryo transfer. B~tL~h Veterinmy Joul~Ta1149, 339-69.

PosTE, G. & KIN~:, N. (1971). Isolation of a herpesvirus fi'om the canine genital tract: association with infertility, abortion and stillbirths. Vetetqnmy Record 88, 229-33.

PRtcr~t.:rr, M. E. (1970). The pathology of disease caused by equine herpesvirus 1. In Proceedings of the ,Second hzternational ('onfi, rence on Equine Infectious Diseases, pp. 2'4-33, eds J. T. BlTans & H. Gerber, Basel: S. Karger AG.

Ro-\NDAI.I., C. C., R',I)FR, F. W., DOLL, E. R. & SllELL, F. S. (1953). Cultivation of equine abortion virus in fetal horse tissue in vitro. American Journal of Pathology 29, 139-53.

Rr:El), D. E., Bl~:~Xl.:t.J., E.J. & Bt'av, R.J. (1973). Systemic torm of infections bovine rhinotracheitis in young calves. Journal of the Ame~4can Vete14na O, Medical Associ- ation 163, 753-5.

RI':EIL D. E., BIt:KNH.[., E.J., LXRSt)N, C. A., KNt'DTSON, ~¢~r. U. & I~aRK~+RmE, C. A. (1971). Infectious bovine rhinotracheitis x, irus-induced abortion: rapid diagnosis by fluorescent antibody technique. American Journal of Veterinary Researeh 32, 1423-6.

Ra~:ED, D. E'., L~×t;l'.w, T . J .Z . , BERt;Vt.~XD, lVl. E. (1979). Bovine abortion associated with mixed Movar 33/63 type herpesvirus and bovine viral diarrhoea virus infection. Comell Veterinarian 69, 54-66.

RZIIIA, H. J., MH-II:NI.I:ITI':R, T. C., OHI.IN(;ER, V. & WH-r.XL.~NN, G. (1986). Herpesx~rns (pseudorabies virus) latency in swine: occurrence and physical state of viral DNA in neural tissues. Virolo~' 155, 600-13.

S.\BINE, ~1., R()I~ERISt)N, G. R. & $,~'rllAl.l.E'f, J. M. (1981). Differentiation of subtypes of equine herpesvirus-1 by ,'estriction endonnclease analysis. ,4 ustralian Veterinmy Journal 57, 148-9.

S.x~o, A. (1985). Analysis of reactivation of latent pseudorabies virus infection in tonsils and gasserian ganglia of pigs. Acta 17roloffica 29, 393---402.

S.\~o, A. & R_qt:.xx~,J. (1976). Latent pseudorabies virus infection in pigs. Acta Virolo~ca 20, 208-14.

SAXEt;.~_.XRO, F. (1966). Isolation and identification of equine rhinopneuluonitis virus (equine abortion virus) fi-om cases of abortion and paralysis. Nordish Veterinoermedecin 18, 504-16.

St:~m-VER, B. (1974). Bovine abortion associated with cytomegalovirns infection. Zentralbl Vete~4naermed 21, 145-51 .

Scm'Lr~H:.tss, P. C., Co~.HNS, J. K. & C..XRXL.XN, J. (1993). Use of an immunoperoxidase techniqtte to detect equine herpesvirus-1 antigen in formalin-fixed paraf- fin-embedded equine fetal tissues. Journal of Vete~na O, Diag~mstic Investigation 5, 12-5.

Scovr, J. C., Dt"rTA, S. K. & M\~cP, A. C. (1983). In vivo harbottring of equine herpesvirus-I in leucocyte populations and sul)populations and their quantit- ation fi'om experimentally infected ponies. American Journal of Vetednmy Research 44, 1344-8.

SHt,~czc, T., IsH~z.-x~:~, R., ISHH, S. et al. (1959). Isolation of equine abortion virus fi'om natural cases of equine abortion in horse kidney cell culture. Japanese Journal of Expe~4mental Medicine 29, 643-9.

S~.-~TER, J. D., BAx~, M., TEWAR~, G. el al. (1994a). Exper- imental infection of specific pathogen-free ponies

with equid herpesvirus-l: detection of infectious virus and viral DNA. In Proceedings of the Seventh Inter- national Conference on Equine Infectious Diseases, pp. 255-260, eds H. Nakajima & W. Plowright. New- market: R&W Publications.

SI.'\TER, J. D., BORCHERS, K., THACKRAY, A. M. & FIEf.D, H.J. (1994b). Tile trigeminal ganglion is a location for equine herpesvirus-1 (EHV-1) latency and reactivation in the horse. Journal of General Virolo~ 75, 2007-16.

S.XIITH, K. C. (1994). Studies on the pathogenesis of abortigenic infection by equid herpesvirus-1 in pregnant pony mares. PhD thesis. University of London.

S,~lrrH, G. H., COWNS, J. K. & CAR,~IAN, J. (1989). Use of an immunoperoxidase test for the detection of bovine herpesvirus-1 in aborted fetal tissue. Journal of Vet- e~4nmy Diagnostic Investigation 1, 39--44.

S.~HrII, K. C., MUMFORD, j . A. & L-XKHANI, K. (1996). A comparison of equid herpesvirus-1 (EHV-1) vascular lesions in the early versus late pregnant equine uterus. Journal of Comparative Patholo~, 114, 231-246.

SMIT}I, I. M., GIIL.~RD, A., CORNER, A. H. & MIT('HELL, D. (1972). The fluorescent antibody technique in the diagnosis of equine rhinopneumonitis virus abortion. Canadian Journal of Comparative Medicine 36, 303--8.

SXHH, K. C., Wl,-rWELL, K. E., BINNS, M. M., DOt.BL C. A., HANNA.'cr, D. & Mt'XWORB,J. A. (1992). Abortion ofvir- ologically negative fetuses following experimental challenge of pregnant pony mares with equid herpesvirus-1. Equine l/ete~naly Journa124, 256-9.

S,~H-H, K. C., WHIqa~'EU., ICE., ML',XlVORD, J. A., GOWER, S. m., HANNANT, D. & TI-2-~RI.E, J. p. (1993). An immu- nohistological study of the uterus of mares following experinaental infection with equid herpesx4rus-1. Equine Vete14naO, Journa125, 36--40.

STEWART, S. E., DAVID-FERREIRA, J., LovEmce, E., L~XNDON, J. & STOCk, N. (1965). Herpeslike virus isolated from neonatal and fetal clogs. Science 148, 1341-8.

STL'DDERT, M.J. (1989). Bovine encephalitis herpesvirus. Veterinmy Recmd 125, 584.

S rt'Dt~VR'r, M.J. & Bt_-XCrZNEV, M. H. (1979). Equine herpesviruses: On the differentiation of respiratory from fetal strains of type 1. Australian Veterinao, Journa155, 488-92.

STt'DDI-R'r, M.J., SIMPSON, T. & ROBZ,XL~XN, B. (1981). Differ- entiation of respiratory and abortigenic isolates of equine herpesvirus 1 by resu-iction endonucleases. Scien a, 214, 562--4.

SWERC:ZEK, T. W. (1990). Non-infectious abortion in mares: etiologic factors and lesions. In Laborato O, Diagnosis of Livestock Abortion, pp. 202-206, ed. C. A. Kirkbride. Anles: Iowa State University Press.

TARI(;AN, S., L-XDDS, P. W. & FOSTER, R. A. (1990). Genital pathology of feral male goats. Australian Veterina D, Jou~m167, 286-90.

TF.XRt.t-, J. P., S,~nTH, K. C., BO~E, M. S.[ BINNS, M. M., LW~:SAV, G.J. & Mt',~IVORD, J. A. (1996). Replication of. equid herpesvirus-1 in the testes and epididymides of ponies following inu-anasal infection and venereal shedding of infectious virus. Journal of Comparative Pathology (in press).

THO,XWSON, K. G. (1987). Caprine herpesvirus infection. Ill Proceedings of a Course in Goat Husband o, and Medi-

268 THE VETERINARY JOURNAL, 153. 3

cine, New Zealand Veterinal'y Association Foundation for Continuing Veterinary Education, Publication No. 106, pp. 199-200. New Zealand: Palmerston North.

Truly, E., Bt'm~or, M., DUBUISSON, J. 8¢ PASTORVT, P.-P. (1989). Bovine herpesvirus--4 (BI-~:-4) infections in cattle. In Helpesvirus Diseases of Cattle, Horses and Pigs, pp. 96-116, ed. G. Wittmann. Boston: Kluwer Aca- demic Publishers.

TURTINEN, L. W., At.kEN, G. P., DARI.IN(;TON, R. W. & BR~: ANS, J. T. (1981). Serological and molecular compari- sons of several equine herpesvirus u, pe 1 strains. A merican Journal of Veterinmy Research 42, 2099-104.

W..u.m'o(;EL, A., ENC;ELS, M., Wu.t), P., STt'NZl, H. & W~a.ER, R. (1981). Caprine herpesvirus infection in Switzer- land: some aspects of its pathogenicity. ~,ntralblattfiir l'?te~4n51wwdezin B 28, 612-23.

W}:L(:H, H. M., BmD(;ES, C. G., LYON, A. M., GRtmTHS, L. & EDIN(,'ro×, N. (1992). Latent equid herpesviruses 1 and 4: detection and distinction using the polymerase chain reaction and co-cultivation fiom lymphoid tissues. Journal of General Virolo~, 73, 261-8.

WFI.t.I"MAN, G., A.x-roiNE, H., BROES, A., CHARI+IFR, G. 8¢ VAN OPOZ,Xt~OS(:H, E. (1984). Varied synlptoms of cases of chronic meuitis associated with a herpesvirus in cattle. Annales de Mddecine i'~;t:t4uaire 128, 65-74.

WE~qtxK, G. H., V..c\ DZR OIRSCII()T, J. T. & Vzmlo~.:vv, J. (1993). Risk of infection with bovine herpesvirus 1 (BHV1): a review. 1.'eterinmy Quarterly 15, 30-3.

WLSW:RVIELO, C. & DIMo(:~, W. W. (1946). The pathology of eqtfine virus abortion. Journal of the American Veter- inan' Medical Association 109, 101-11.

WHrI'W'ELL, K. E., GOWZR, S. M. & SMrrH, K. C. (1992). An immunoperoxidase method applied to the diagnosis

of equine herpesvirus abortion, using conventioqal and rapid microwave techniqtms. Equine Veteriualy .Journal 24, 10-2.

WHvrwEI.t., K. E., Bowv..~,.l.M. & H:~NN.-XN'r, D. (1995a). A search for antibody to equine herpesvirus-I in equine fetuses. In Proceerlinff~ of the Seventh lulerualional Confer- ence on Equine b~fectious Diseases, pp. 339-40, eds H. Nakajima & W. Plowright, Newmarket: R&W Pub- lications.

WHN'WELL, K. E., SMrt-i;, K. C., StNCl,UR, R. & Mt'MFORI), J. A. (19951)). Fetal lesions in spontaneous EHV-4 a b o f tion in mares. In Proceedinff~ of the Seventh luternalional Conference on Equine h![~'ctious Diseases, pp. 354, eds H. Nakajima & W. Plowright. Newmarket: R&W Pub- lications.

Wm-.~L.XNy, G., .J..xr~ct~tr~, J. & AJH., R. (1980). Multipli- cation and distribution of Aujeszky's disease (pseudorabies) virus in vaccinated and non-vaccinated pigs after intranasal infection. Archives of l.Trolo~, 66, 227-41/.

W()III.(;I-.x, IUTII, K., LESI.IE, P. F., REI-LL D. E. & S.xtm't', D. K. (1978). Pseudorabies virus associated with abortion in swine..]ourual of the American Vele~4naty Medical Association 172, 478-9.

Y-\NA(;ISAWA, T., AZI-TAKA, M., MIDORO, K., TAg.UtASIH, R., Ft'Im'AP~-X, K. & SAWA, K. (1987). Fatal herpesvirus infection ill a litter of puppies..]apanese.]0urua/of Vet- erinmy Science 49, 519-22.

Yall-s, W. D. G. (1982). A review of infectious bovine rhilaotracheitis, shipping fever pneumonia and viral- bacteria synergism in respiratol 3, disease of cattle. Canadian flmrnal of Com/mralive Medicine46, 225-63.

(Aca,pled Jbr publication 23.]au ualy 1996)

Herpes Viral Abortion in Domestic Animals

Documents

Transcript of Herpes Viral Abortion in Domestic Animals