Msc Bub 103 Unit 9 Virus 51
Transcript of Msc Bub 103 Unit 9 Virus 51
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VIROLOGY
Viruses are smaller and less complex than bacteria. As science became aware of
the role of the viruses in human disease, the techniques of bacteriology were modified toaccomodate the viruses and the discipline of virology grew up within bacteriology.
Viruses are the cause of many diseases in humans ranging from AIDS and cancer
to the common cold. Microbiologists have developed vaccines for many viral diseases,
but haven not been as successful in discovery of treatments for the diseases. It is theopposite in bacteriology, at least since the discovery of antibiotics.
Virus Structure
Viruses consist of nucleic acid (DNA or RNA) surrounded by a protein coat
called a capsid. The capsid is made up of individual structural subunits
called capsomeres. Individual capsomeres are arranged to form a capsid which encloses
the nucleic acid (DNA or RNA) of the virus. Some viruses have additional structuralfeatures, such as the envelope of animal viruses or the tail of bacteriophages. Many
animal viruses also contain an envelope, which is partly derived from the host cellmembtrane but which always contains unique viral proteins (spikes).
poliovirus herpes virus tobacco mosaic
virus
influenza virus
Figure 9.1. The most common viral morphologies. A naked icosahedral virus, an
enveloped icosahedral virus, a naked helical virus and an enveloped helical virus.
General Features of Viruses
Viruses are considered obligate intracellular parasites because they require a hostcell in order to replicate. The host cell may be any form of eucaryote or procaryote.
Viruses are noncellular entities that are not considered as living by most
microbiologists. They are very different from cells. The viruses lack membranes andcannot produce their energy since, they lack enzymes for metabolic functions. They also
lack ribosomes required for protein synthesis.
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The general features of viruses are outlined in the table below.
Table 9. 1. General Features of Viruses
Viral Features Properties
1. Small size Viruses cannot be viewed with a light microscopepass through filters that retain bacteria. Viral sizes rangebetween 0.1-0.3 micrometers
2. Characteristic shapes Spherical (complex), helical, rod or polyhedral,sometimes with tails or envelopes. Most common
polyhedron is the icosahedron which as 20 triangular
faces.
3. Obligate intracellular
parasites
Viruses do not contain within their coats the machinery
for replication. For this they depend upon a host cell for
their existence as obligate intracellular parasites. Eachvirus can only infect certain species of cells. This refers
to the virus host range.4. No built-in metabolic
machinery
Viruses have no metabolic enzymes and cannot generate
their own energy.
5. No ribosome Viruses cannot synthesize their own proteins. Theyutilize host cell ribosomes for this during replication.
6. Only one type of nucleicacid
Viruses contain either DNA or RNA (never both) astheir genetic material. The nucleic acid can be single-
stranded or double stranded.
7. Do not grow in size Unlike cells, viruses do not grow in size and mass
leading to a division process. Rather viruses grow by
separate synthesis and assembly of their components
resulting in production of mature viruses.
Classification of Viruses
Viruses are classified on the basis of host range, morphology (size, shape), type of
nucleic acid (DNA, RNA, single-stranded, double-stranded, linear, circular, segmented,etc.) and occurrence of auxilliary structures such as tails or envelopes.
Host range refers to the type of host cell in which it grows. Depending upon the
host the viruses prefer, they can be broadly arranged into four groups. They are:
1. bacterial viruses (bacteriophage),2. animal viruses,
3. insect viruses (bacculoviruses) and
4. plant viruses.
Hosts of viruses
Hosts of viruses include all classes of cellular organisms described to date:
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General Host Range
Prokaryotes: Archaea Bacteria Mycoplasma Spiroplasma
Eukaryotes: Algae Plants Prortozoa Fungi
Invertebrates Vertebrates
Figure 2. Shapes and comparative sizes of different groups of viruses.A. Smallpox virus B. Orf virus C. Rhabdovirus D. Paramyxovirus
E. Bacteriophage T2 F. Flexuous-tailed
bacteriophage
G. Herpes virus H. Adenovirus
I. Influenza virus J. Filamentousflexuous virus
K. Tobacco mosaic virus L. Polyoma/papillomavirus
M. Alflafa mosaic virus N. Poliovirus O. Bacteriophage phiX174
Viruses have three fundamental morphology types:
1. Polygonal, the most common polygon being the icosahedron (E, F, G, H, L, N);
2. Helical, wherein the capsomeres assemble as a helix enclosing the nucleic acid)(B, D, I, J, K, M)
3. Complex, wherein the proteins are laid down in patches or layers (A). Some
animal viruses have envelopes which enclose their nucleocapsid (D, G, I). Theenvelopes are embedded with viral proteins that secure their entry and exit in
cells. Only bacteriophages have tails which are used for adsorption and
penetration of their host cell.
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Classification of Viruses
Classical virus classification schemes have been based on the consideration offour major properties of viruses:
1. The type of nucleic acid which is found in the virion (RNA or DNA)2. The symmetry and shape of the capsid
3. The presence or absence of an envelope
4. The size of the virus particle
More recent classification systems adopted by the International Committee on
Viral Taxonomy (ICTV) is based on the nature of viral genome as the primary
determinant. Furthermore, there is a drift towards the use of genomics for virusclassification that is sequence analysis of the viral genome, and comparison to other
known viral sequences.
The naming system for viruses that has been adopted by the ICTV is very usefulfor animal viruses, and is widely used. Latinized virus family names start with capital
letters and end with the suffix viridae (e.g., Herpesviridae). These formal names areoften used interchangably with the common names for viruses (e.g., herpesviruses).
The system makes use of a series of ranked taxons, with the:
Order (-virales) being the highest currently recognised.
Family (-viridae)
Subfamily (-virinae)
Genus (-virus)
Species (name of virus)
For example, the Ebola virus is classified as:
Order Mononegavirales
Family Filoviridae
Genus Filovirus
Species: Ebola virus Zaire
The most important taxonomic criteria are:
Host Organism(s)
Particle Morphology
Genome Typealthough a number of other criteria - such as disease symptoms, antigenicity, protein
profile, host range, etc. are important in precise identification, consideration of theabove three criteria are sufficient in most cases to allow identification of a virus down to
familial if not generic level.
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The Properties used for Classifying Viruses are as follows:
S.No Primary Characteristics Secondary Characteristics
1. Chemical nature of nucleic acid: RNA or
DNA; single or double stranded; single orsegmented genome; (+) or (-) strand ;molecular weight .
Host range:
Host species, specific hosttissues or cell types.
2. Structure of virion : Helical , icosahedral, or
complex; naked or enveloped, complexity;number of capsomers for icosahedral virions,
diameter of nucleo-capsids for helical viruses.
Mode of transmission:
Ex: faeces.
3.. Site of replication:Nucleus or cytoplasm Specific surface structures:Ex: antigenic properties
Certain virus families / groupings cross kingdom or phylum boundaries
The virus families infecting two kingdoms of organisms are:
Bunyaviridae (animals and plants)
Partitiviridae (plants and fungi)
Reoviridae (animals and plants)
Rhabdoviridae (animals and plants)
Phycodnaviridae (protozoa and plants)
Picornoviridae (plants and animals - tentative)
Totiviridae (protozoa / fungi and insects - tentative)
Virus families infecting across different phyla (all infecting insects and vertebrates)are:
Flaviviridae
Iridiviridae
Parvoviridae
Poxviridae
Togaviridae
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International Committee on Viral Taxonomy (ICTV) Classification System
Group I: dsDNA Viruses
OrderCaudovirales - Tailed BacteriophagesFamily(Subfamily) Genus Type Species H
Myoviridae T4-like viruses Enterobacteria phage
T4
Bacte
P1-like viruses Enterobacteria phage
P1
Bacte
P2-like viruses Enterobacteria phage
P2
Bacte
Mu-like viruses Enterobacteria phage
Mu
Bacte
SP01-like viruses Bacillus phage SP01 Bacte
H-like viruses Halobacterium virusH
Bacte
Podoviridae T7-like viruses Enterobacteria phage
T7
Bacte
P22-like viruses Enterobacteria phage
P22
Bacte
29-like viruses Bacillus phage 29 Bacte
N4-like viruses Enterobacteria phage
N4
Bacte
Siphoviridae -like viruses Enterobacteria phage
Bacte
T1-like viruses Enterobacteria phageT1
Bacte
T5-like viruses Enterobacteria phage
T5
Bacte
L5-like viruses Mycobacterium phage
L5
Bacte
c2-like viruses Lactococcus phage c2 Bacte
M1-like viruses Methanobacterium
virus M1
Bacte
C31-like viruses Streptomyces phage
C31
Bacte
N15-like viruses Enterobacteria phageN15
Bacte
Family(Subfamily) Genus Type Species H
Ascoviridae Ascovirus Spodoptera frugiperda
ascovirus
Inver
Adenoviridae Atadenovirus Ovine adenovirus D Verte
Aviadenovirus Fowl adenovirus A Verte
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Mastadenovirus Human adenovirus CVerte
Siadenovirus Frog adenovirus Verte
Asfarviridae Asfivirus African swine fever
virus
Verte
Baculoviridae Nucleopolyhedrovirus Autographa
californicanucleopolyhedrovirus
Inver
Granulovirus Cydia pomonella
granulovirus
Inver
Corticoviridae Corticovirus Alteromonas phage
PM2
Bacte
Fuselloviridae Fusellovirus Sulfolobus virus SSV1 Archa
Guttaviridae Guttavirus Sulfolobus virus
SNDV
Archa
Herpesviridae
:
Ictalurivirus Ictalurid herpesvirus 1 Verte
Alphaherpesvirinae Mardivirus Gallid herpesvirus 2 Verte
Simplexvirus Human herpesvirus 1VerteVaricellovirus Human herpesvirus 3 Verte
Iltovirus Gallid herpesvirus 1 Verte
Betaherpesvirinae Cytomegalovirus Human herpesvirus 5 Verte
Muromegalovirus Murine herpesvirus 1 Verte
Roseolovirus Human herpesvirus 6Verte
Gammaherpesvirina
e
Lymphocryptovirus Human herpesvirus 4 Verte
Rhadinovirus Simian herpesvirus 2Verte
Iridoviridae Iridovirus Invertebrate irid
virus 6
Inver
Chloriridovirus Invertebrate iridescent
virus 3
Inver
Ranavirus Frog virus 3 Verte
Lymphocystivirus Lymphocystis disease
virus 1
Verte
Megalocytivirus Infectious spleen and
kidney necrosis virus
Verte
Lipothrixviridae Alphalipothrixvirus Thermoproteus virus 1Archa
Betalipothrixvirus Sulfolobus
mislandicus
filamentous virus
Archa
Gammalipothrixvirus Acidianus filamentous
virus1
Archa
Nimaviridae Whispovirus White spot syndrome
virus 1
Inver
Mimivirus Acanthamoeba
polyphaga mimivirus
Proto
Verte
Polyomaviridae Polyomavirus Simian virus 40 Verte
Papillomaviridae Alphapapillomavirus Human Verte
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papillomavirus 32
Betapapillomavirus Human
papillomavirus 5
Verte
Gammapapillomavirus Human
papillomavirus 4
Verte
Deltapapillomavirus European elkpapillomavirus
Verte
Epsilonpapillomavirus Bovin papillomavirus
5
Verte
Zetapapillomavirus Equine papillomavirus
1
Verte
Etapapillomavirus Fringilla coelebs
papillomavirus
Verte
Thetapapillomavirus Psittacus erithacus
timneh papillomavirus
Verte
Iotapapillomavirus Mastomys natalensis
papillomavirus
Verte
Kappapapillomavirus Cottontail rabbit
papillomavirus
Verte
Lambdapapillomavirus Canine oral
papillomavirus
Verte
Mupapillomavirus Human
papillomavirus 1
Verte
Nupapillomavirus Human
papillomavirus 41
Verte
Xipapillomavirus Bovine papillomavirus
3
Verte
Omikronpapillomavirus
Phocoena spinipinnispapillomavirus
Verte
Pipapillomavirus Hamster oral
papillomavirus
Verte
Phycodnaviridae Chlorovirus Paramecium bursaria
Chlorella virus 1
Algae
Prasinovirus Micromonas pusilla
virus SP1
Algae
Prymnesiovirus Chryosochromomuli
a brevifilium virus
PW1
Algae
Phaeovirus Extocarpus siliculosusvirus 1
Algae
Coccolithovirus Emiliania huxleyi
virus 86
Algae
Raphidovirus Heterosigms akashiwo
virus 01
Algae
Plasmaviridae Plasmavirus Acholeplasma pha
L2
Myco
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Polydnaviridae Ichnovirus Campoletis sonor
ichnovirus
Inver
Bracovirus Cotesia melanoscela
brachovirus
Inver
Poxviridae: Chordopoxvirinae Orthopoxvirus Vaccinia virus Verte
Parapoxvirus Orf virus Verte Avipoxvirus Fowlpox virus Verte
Capripoxvirus Sheeppox virus Verte
Leporipoxvirus Myxoma virus Verte
Suipoxvirus Swinepox virus Verte
Molluscipoxvirus Molluscum
contagiosum virus
Verte
Yatapoxvirus Yaba monkey tumor
virus
Verte
Entomopoxvirinae Entomopoxvirus A Melolontha
melolontha
entomopoxvirus
Inver
Entomopoxvirus B Amsacta moorei
entomopoxvirus
Inver
Entomopoxvirus C Chironomus luridus
entomopoxvirus
Inver
Rhizidovirus Rhizidomyces virus Fungi
Rudiviridae Rudivirus Sulfolobus virus
SIRV1
Archa
Tectiviridae Tectivirus Enterobacteria phage
PRD1
Bacte
Group II: ssDNA Viruses
Family(Subfamily) Genus Type Species Hosts
Anellovirus Torque teno virus Vertebrates
Circoviridae Circovirus Porcine circovirus Vertebrates
Gyrovirus Chicken anemia virus Vertebrates
Geminiviridae Mastrevirus Maize streak virus Plants
Curtovirus Beet curly top virus Plants
Topocuvirus Tomato pseudo-curly
top virus
Plants
Begomovirus Bean golden mosaic
virus
Plants
Inoviridae Inovirus Enterobacteria phage
M13
Bacteria
Plectrovirus Acholeplasma phage
MV-L51
Bacteria
Microviridae Microvirus Enterobacteria X174 Bacteria
Spiromicrovirus Spiroplasma phage 4 Spiroplasma
Bdellomicrovirus Bdellovibrio phage
MAC1
Bacteria
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Chlamydiamicroviru
s
Chlamydia phage 1 Bacteria
Nanoviridae Nanovirus Subterranean clover
stunt virus
Plants
Babuvirus Banana bunchy top
virus
Plants
Parvoviridae
:
Parvovirinae Parvovirus Mice minute virus Vertebrates
Erythrovirus B19 virus Vertebrates
Dependovirus Adeno-associated virus
2
Vertebrates
Amdovirus Aleutian mink disease
virus
Vertebrates
Bocavirus Bovine parvovirus Vertebrates
Densovirina
e
Densovirus Junonia coenia
densovirus
Invertebrates
Iteravirus Bombyx mori
densovirus
Invertebrates
Brevidensovirus Aedes aegypti
densovirus
Invertebrates
Pefudensovirus Periplanta fuliginosa
densovirus
Invertebrates
Group III: dsRNA Viruses
Family
(Subfamily)
Genus Type Species Hosts
Birnaviridae Aquabirnavirus Infectious pancreatic necrosis
virus
Vertebrates
Avibirnavirus Infectious bursal disease virus Vertebrates
Entomobirnavirus
Drosophila X virus Invertebrates
Chrysoviridae Chrysovirus Penicillium chrysogenum virus Fungi
Cystoviridae Cystovirus Pseudomonas phage 6 Bacteria
Endornavirus Vicia faba endornavirus Plants
Hypoviridae Hypovirus Cryphonectria hypovirus 1-
EP713
Fungi
Partitiviridae Partitivirus Atkinsonella hypoxylon virus Fungi
Alphacryptovirus White clover cryptic virus 1 Plants
Betacryptovirus White clover cryptic virus 2 Plants
Reoviridae Orthoreovirus Mammalian orthoreovirus Vertebrates
Orbivirus Bluetongue virus Vertebrates
Rotavirus Rotavirus A Vertebrates
Coltivirus Colorado tick fever virus Vertebrates
Aquareovirus Golden shiner virus Vertebrates
Seadornavirus Banna virus Vertebrates
Cypovirus Cypovirus 1 Invertebrates
Idnoreovirus Idnoreovirus 1 Invertebrates
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Fijivirus Fiji disease virus Plants
Phytoreovirus Wound tumor virus Plants
Oryzavirus Rice ragged stunt virus Plants
Mycoreovirus Mycoreovirus 1 Fungi
Totiviridae Totivirus Saccharomyces cerevisiae virus
L-A
Fungi
Giardiavirus Giardia lamblia virus Protozoa
Leishmaniavirus Leishmania RNA virus 1-1 Protozoa
Group IV: (+)sense RNA Viruses
OrderNidovirales - "Nested" Viruses
Family
(Subfamily)
Genus Type Species Hosts
Arteriviridae Arterivirus Equine arteritis virus Vertebrates
Coronaviridae Coronavirus Infectious bronchitis virus Vertebrates
Torovirus Equine torovirus Vertebrates
Roniviridae Okavirus Gill-associated virus Vertebrates
Family
(Subfamily)
Genus Type Species Hosts
Astroviridae Avastrovirus Turkey astrovirus Vertebrates
Mamastrovirus Human astrovirus Vertebrates
Barnaviridae Barnavirus Mushroom bacilliform virus Fungi
Benyvirus Beet necrotic yellow vein virus Plants
Bromoviridae Alfamovirus Alfalfa mosaic virus Plants
Bromovirus Brome mosaic virus Plants
Cucumovirus Cucumber mosaic virus Plants
Ilarvirus Tobacco streak virus Plants
Oleavirus Olive latent virus 2 Plants
Caliciviridae Lagovirus Rabbit haemorrhagic disease virus Vertebrates
Norovirus Norwalk virus Vertebrates
Sapovirus Sapporo virus Vertebrates
Vesivirus Swine vesicular exanthema virus VertebratesCheravirus Cherry rasp leaf virus Plants
Closteroviridae Ampelovirus Grapevine leafroll-associated virus 3 Plants
Closterovirus Beet yellows virus Plants
Comoviridae Comovirus Cowpea mosaic virus Plants
Fabavirus Broad bean wilt virus 1 Plants
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Nepovirus Tobacco ringspot virus Plants
Dicistroviridae Cripavirus Cricket paralysis virus Invertebrates
Flaviviridae Flavivirus Yellow fever virus Vertebrates
Pestivirus Bovine diarrhea virus 1 Vertebrates
Hepacivirus Hepatitis C virus Vertebrates
Flexiviridae Potexvirus Potato virus X Plants
Mandarivirus Indian citrus ringspot virus Plants
Allexivirus Shallot virus X Plants
Carlavirus Carnation latent virus Plants
Foveavirus Apple stem pitting virus Plants
Capillovirus Apple stem grooving virus Plants
Vitivirus Grapevine virus A Plants
Trichovirus Apple chlorotic leaf spot virus Plants
Furovirus Soil-borne wheat mosaic virus Plants
Hepevirus Hepatitis E virus Vertebrates
Hordeivirus Barley stripe mosaic virus Plants
Idaeovirus Rasberry bushy dwarf virus Plants
Iflavirus Infectious flacherie virus Invertebrates
Leviviridae Levivirus Enterobacteria phage MS2 Bacteria
Allolevivirus Enterobacteria phage Q Bacteria
Luteoviridae Luteovirus Cereal yellow dwarf virus-PAV Plants
Polerovirus Potato leafroll virus Plants Enamovirus Pea enation mosaic virus-1 Plants
Machlomovirus Maize chlorotic mottle virus Plants
Marnaviridae Marnavirus Heterosigma akashiwo RNA virus Fungi
Narnaviridae Narnavirus Saccharomyces cerevisiae narnavirus 20SFungi
Mitovirus Cryphonectria parasitica mitovirus 1-NB631
Fungi
Nodaviridae Alphanodoavirus Nodamura virus Invertebrates
Betanodovirus Striped jack nervous necrosis virus Vertebrates
Pecluvirus Peanut clump virus Plants
Ourmiavirus Ourmia melon virus Plants
Picornaviridae Enterovirus Poliovirus Vertebrates
Rhinovirus Human rhinovirus A Vertebrates
Hepatovirus Hepatitis A virus Vertebrates
Cardiovirus Encephalomyocarditis virus Vertebrates
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Aphthovirus Foot-and-mouth disease virus O Vertebrates
Parechovirus Human parechovirus Vertebrates
Erbovirus Equine rhinitis B virus Vertebrates
Kobuvirus Aichi virus Vertebrates
Teschovirus Porcine teschovirus Vertebrates
Pomovirus Potato mop-top virus Plants
Potyviridae Potyvirus Potato virus Y Plants
Ipomovirus Sweet potato mild mottle virus Plants
Macluravirus Maclura mosaic virus Plants
Rymovirus Ryegrass mosaic virus Plants
Tritimovirus Wheat streak mosaic virus Plants
Bymovirus Barley yellow mosaic virus Plants
Sadwavirus Satsuma dwarf virus Plants
Sequiviridae Sequivirus Parsnip yellow fleck virus Plants
Waikavirus Rice tungro spherical virus Plants
Sobemovirus Southern bean mosaic virus Plants
Tetraviridae Betatetravirus Nudaurelia capensis virus Invertebrates
Omegatetravirus Nudaurelia capensis virus Invertebrates
Tobamovirus Tobacco mosaic virus Plants
Tobravirus Tobacco rattle virus Plants
Tombusviridae Tombusvirus Tomato bushy stunt virus Plants
Avenavirus Oat chlorotic stunt virus Plants Aureusvirus Pothos latent virus Plants
Carmovirus Carnation mottle virus Plants
Dainthovirus Carnation ringspot virus Plants
Machlomovirus Maize chlorotic mottle virus Plants
Necrovirus Tobacco necrosis virus Plants
Panicovirus Panicum mosaic virus Plants
Togaviridae Alphavirus Sindbis virus Vertebrates
Rubivirus Rubella virus Vertebrates
Tymoviridae Maculavirus Grapevine fleck virus Plants
Marafivirus Maize rayado fino virus Plants
Tymovirus Turnip yellow mosaic virus Plants
Umbravirus Carrot mottle virus Plants
Group V: (-)sense RNA Viruses
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Order Mononegavirales
Family(Subfamily) Genus Type Species Hosts
Bornaviridae Bornavirus Borna disease virusVertebrates
Filoviridae Marburgvirus Lake Victoria
marburgvirus
Vertebrates
Ebolavirus Zaire ebolavirus Vertebrates
Paramyxoviridae Paramyxovirinae Avulavirus Newcastle disease virus Vertebrates
Henipavirus Hendra virus Vertebrates
Morbillivirus Measles virus Vertebrates
Respirovirus Sendai virus Vertebrates
Rubulavirus Mumps virus Vertebrates
Pneumovirinae Pneumovirus Human respiratorysyncytial virus
Vertebrates
Metapneumovirus Avian pneumovirus Vertebrates
Rhabdoviridae Vesiculovirus Vesicular stomatitis
Indiana virusVertebrates,Invertebrates
Lyssavirus Rabies virus Vertebrates
Ephemerovirus Bovine ephemeral fevervirus
Vertebrates,
Invertebrates
Novirhabdovirus Infectious haematopoetic
necrosis virusVertebrates
Cytorhabdovirus Lettuce necrotic yellows
virus
Plants,
Invertebrates
Nucleorhabdovirus Potato yellow dwarf
virusPlants,
Invertebrates
Family(Subfamily) Genus Type Species Hosts
Arenaviridae Arenavirus Lymphocytic
choriomeningitis virus
Vertebrates
Bunyaviridae Orthobunyavirus Bunyamwera virus Vertebrates
Hantavirus Hantaan virus Vertebrates
Nairovirus Nairobi sheep disease
virusVertebrates
Phlebovirus Sandfly fever Sicilian
virus
Vertebrates
Tospovirus Tomato spotted wilt virus Plants
Deltavirus Hepatitis delta virusVertebrates
Ophiovirus Citrus psorosis virus Plants
Orthomyxoviridae Influenza A virus Influenza A virus Vertebrates
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Influenza B virus Influenza B virus Vertebrates
Influenza C virus Influenza C virus Vertebrates
Isavirus Infectious salmonanemia virus
Vertebrates
Thogotovirus Thogoto virus VertebratesTenuivirus Rice stripe virus Plants
Varicosaivirus Lettuce big-vein
associated virusPlants
Group VI: RNA Reverse Transcribing Viruses
Family
(Subfamily)Genus Type Species Hosts
Retroviridae Alpharetrovirus Avian leukosis virus Vertebrates
Betaretrovirus Mouse mammary tumor virus Vertebrates
Gammaretrovirus Murine leukemia virus VertebratesDeltaretrovirus Bovine leukemia virus Vertebrates
Epsilonretrovirus Walley dermal sarcoma virus Vertebrates
Lentivirus Human immunodeficiency virus 1 Vertebrates
Spumavirus Human spumavirus Vertebrates
Metaviridae Metavirus Saccharomyces cerevisiae Ty3 virus Fungi
Errantivirus Drosophila melanogaster gypsy virus Invertebrates
Pseudoviridae Pseudovirus Saccharomyces cerevisiae Ty1 virus Invertebrates
Hemivirus Drosophila melanogaster copia virus Invertebrates
Group VII: DNA Reverse Transcribing Viruses
Family
(Subfamily)
Genus Type Species Hosts
Hepadnaviridae Orthohepadnavirus Hepatitis B virus Vertebrates
Avihepadnavirus Duck hepatitis B virus Vertebrates
Caulimoviridae Caulimovirus Cauliflower mosaic virus Plants
Badnavirus Commelina yellow mottle virus Plants
Cavemovirus Cassava vein mosaic virus Plants
Petuvirus Petunia vein clearing virus Plants
Soymovirus Soybean chlorotic mottle virus Plants
Tungrovirus Rice tungro bacilliform virus Plants
Subviral Agents: Viroids
Family(Subfamily) Genus Type Species Hosts
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Pospiviroidae Pospiviroid Potato spindle tuber viroid Plants
Hostuviroid Hop stunt viroid Plants
Cocadviroid Coconut cadang-cadang viroid Plants
Apscaviroid Apple scar skin viroid Plants
Coleviroid Coleus blumei viroid 1 Plants
Avsunviroidae Avsunviroidae Avocado sunblotch viroid Plants
Pelamonviroid Peach latent mosaic viroid Plants
The Bacteriophages
Viruses that attack bacteria were observed by Twort and d'Herelle in 1915 and1917. They observed that broth cultures of certain intestinal bacteria could be dissolved
by addition of a bacteria-free filtrate obtained from sewage. The lysis of the bacterial
cells was said to be brought about by a virus.
Every known bacterium is subject to an infection by viruses orbacteriophages("phage" from Gr. "phagein" meaning "to eat"). But at research level more
work has been done on the phages that infectE. coli. Ex: the T-phages and phage lambda.
Like most viruses, bacteriophages carry only the genetic information needed for
replication of their nucleic acid and synthesis of their protein coats. When phages infecttheir host cell they utilize the bacterial precursors, energy and ribosomes to replicate their
nucleic acid and to produce the protective protein coat.
Bacterial cells can undergo one or two types of infections by bactriophages. They
are termed as lytic infections or lysogenic (temperate) infections. A group seven phagesknown as the T-phages cause lytic infections inE. coli. Whereas, phage lambda causes
lysogenic infections.
Composition and Structure of Bacteriophage
A. Composition
Although different bacteriophages may contain different materials they all contain
nucleic acid and protein.
Depending upon the phage, the nucleic acid can be either DNA or RNA but not
both and it can exist in various forms. The nucleic acids of phages often contain unusualor modified bases. These modified bases protect phage nucleic acid from nucleases that
break down host nucleic acids during phage infection. The size of the nucleic acid varies
depending upon the phage. The simplest phages only have enough nucleic acid to codefor 3-5 average size gene products while the more complex phages may code for over
100 gene products.
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The number of different kinds of protein and the amount of each kind of protein
in the phage particle will vary depending upon the phage. The simplest phage have many
copies of only one or two different proteins while more complex phages may have manydifferent kinds. The proteins function in infection and to protect the nucleic acid from
nucleases in the environment.
B. Structure
Bacteriophage come in many different sizes and shapes. The basic structural
features of bacteriophages (Ex: phage T4).
Figure 4. Bacteriophage T4
1. Size - T4 is among the largest phages; it is approximately 200 nm long and 80-100 nm
wide. Other phages are smaller. Most phages range in size from 24-200 nm in length.
2. Head or Capsid - All phages contain a head structure which can vary in size and shape.Some are icosahedral (20 sides) others are filamentous. The head or capsid is composed
of many copies of one or more different proteins. Inside the head is found the nucleicacid. The head acts as the protective covering for the nucleic acid.
3. Tail - Many but not all phages have tails attached to the phage head. The tail is ahollow tube through which the nucleic acid passes during infection. The size of the tail
can vary and some phages do not even have a tail structure. In the more complex phages
like T4 the tail is surrounded by a contractile sheath which contracts during infection ofthe bacterium. At the end of the tail the more complex phages like T4 have a base plate
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and one or more tail fibers attached to it. The base plate and tail fibers are involved in the
binding of the phage to the bacterial cell. Not all phages have base plates and tail fibers.
In these instances other structures are involved in binding of the phage particle to thebacterium.
Phage multiplication cycle
Lytic or Virulent Phages
1. Definition - Lytic or virulent phages are phages which can only multiply on bacteriaand kill the cell by lysis at the end of the life cycle.
2. Life cycle - The life cycle of a lytic phage is illustrated:
Eclipse period - During the eclipse phase, no infectious phage particles can be foundeither inside or outside the bacterial cell. The phage nucleic acid takes over the host
biosynthetic machinery and phage specified m-RNA's and proteins are made. There is anorderly expression of phage directed macromolecular synthesis. Early m-RNA's code forearly proteins needed for phage DNA synthesis and for shutting off host DNA, RNA and
protein biosynthesis. In some cases the early proteins actually degrade the host
chromosome. After phage DNA is made late m-RNA's and late proteins are made. Thelate proteins are the structural proteins of the phage as well as the proteins needed for
lysis of the bacterial cell.
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Intracellular Accumulation Phase - In this phase the nucleic acid and structural
proteins that have been made are assembled and infectious phage particles accumulate
within the cell.
Lysis and Release Phase - After a while the bacteria begin to lyse due to the
accumulation of the phage lysis protein and intracellular phage are released into themedium. The number of particles released per infected bacteria may be as high as 1000.
The lytic infections
Before phage infection, the bacterial cell is involved in replication of its own
DNA and transcription and translation of its own genetic information to carry out
biosynthesis, growth and cell division. After phage attack, the viral DNA takes over the
machinery of the host cell and uses it to produce the nucleic acids and proteins needed for
production of new virus particles. Viral DNA replaces the host cell DNA as a templatefor both replication (to produce more viral DNA) and transcription (to produce viral
mRNA). Viral mRNAs are then translated, using host cell ribosomes, tRNAs and aminoacids, into viral proteins such as the coat or tail proteins. The process of DNA replication,
synthesis of proteins, and viral assembly is a carefully coordinated.
The overall process of lytic infection and discussion is diagrammed below:
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Figure 4. The lytic cycle of a bacterial virus, e.g. bacteriophage T4.
The first step in the replication of the phage in its host cell is called adsorption.The phage particle undergoes a chance collision at a chemically complementary site on
the bacterial surface, then adheres to that site by means of its tail fibers.
Following adsorption, the phage injects its DNA into the bacterial cell. The tailsheath contracts and the core is driven through the wall to the membrane. This process is
called penetration and it may be both mechanical and enzymatic. Phage T4 packages a
bit of lysozyme in the base of its tail from a previous infection and then uses thelysozyme to degrade a portion of the bacterial cell wall for insertion of the tail core. The
DNA is injected into the periplasm of the bacterium.
Immediately after injection of the viral DNA there is a process initiatedcalled synthesis of early proteins. This refers to the transcription and translation of asection of the phage DNA to make a set of proteins that are needed to replicate the phage
DNA. Among the early proteins produced are a repair enzyme to repair the hole in the
bacterial cell wall, a DNAase enzyme that degrades the host DNA into precursors of
phage DNA, and a virus specific DNA polymerase that will copy and replicate phageDNA. During this period the cell's energy-generating and protein-synthesizing abilities
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are maintained, but they have been subverted by the virus. The result is the synthesis ofseveral copies of the phage DNA.
The next step is the synthesis of late proteins. Each of the several replicatedcopies of the phage DNA can now be used for transcription and translation of a second
set of proteins called the late proteins. The late proteins are mainly structural proteinsthat make up the capsomeres and the various components of the tail assembly. Lysozyme
is also a late protein that will be packaged in the tail of the phage and be used to escapefrom the host cell during the last step of the replication process.
Having replicated all of their parts, there follows an assembly process. The
proteins that make up the capsomeres assemble themselves into the heads and "reel in" a
copy of the phage DNA. The tail and accessory structures assemble and incorporate a bitof lysozyme in the tail plate. The viruses arrange their escape from the host cell during
the assembly process.
While the viruses are assembling, lysozyme is being produced as a late viralprotein. Part of this lysozome is used to escape from the host cell by lysing the cell wall
peptiodglycan from the inside. This accomplishes the lysis of the host cell and the
release of the mature viruses, which spread to nearby cells, infect them, and complete
the cycle. The life cycle of a T-phage takes about 25-35 minutes to complete. Because thehost cells are ultimately killed by lysis, this type of viral infection is referred to a lytic
infection.
Lysogenic Infections
Lysogenic or temperate infection rarely results in lysis of the bacterial host cell.
Lysogenic viruses, such as lambda which infectsE. coli, have a different strategy thanlytic viruses for their replication. After penetration, the virus DNA integrates into the
bacterial chromosome and it becomes replicated every time the cell duplicates itschromosomal DNA during normal cell division. The life cycle of a lysogenic
bacteriophage is illustrated below.
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Figure 7. The lysogenic cycle of a temperate bacteriophage such as lambda.
Temperate viruses usually do not kill the host bacterial cells they infect. Their
chromosome becomes integrated into a specific section of the host cell chromosome.Such phage DNA is called prophage and the host bacteria are said to be lysogenized. In
the prophage state all the phage genes except one are repressed. None of the usual early
proteins or structural proteins are formed.
The phage gene that is expressed is an important one because it codes for thesynthesis of a repressor molecule that prevents the synthesis of phage enzymes and
proteins required for the lytic cycle. If the synthesis of the repressor molecule stops or if
the repressor becomes inactivated, an enzyme encoded by the prophage is synthesizedwhich excises the viral DNA from the bacterial chromosome. This excised DNA (the
phage genome) can now behave like a lytic virus, that is to produce new viral particlesand eventually lyse the host cell. This spontaneous derepression is a rare event
occurring about one in 10,000 divisions of a lysogenic bacterium., but it assures that newphage are formed which can proceed to infect other cells.
Usually it is difficult to recognize lysogenic bacteria because lysogenic and nonlysogenic
cells appear identical. But in a few situations, the prophage supplies genetic information
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such that the lysogenic bacteria exhibit a new characteristic (new phenotype), not
displayed by the nonlysogenic cell, a phenomenon called lysogenic conversion.
Significance of Lysogeny
Model for animal virus transformation - Lysogeny is a model system for virustransformation of animal cells
Lysogenic conversion - When a cell becomes lysogenized, occasionally extra
genes carried by the phage get expressed in the cell. These genes can change the
properties of the bacterial cell. This process is called lysogenic or phage conversion. Thiscan be of significance clinically. e.g. Lysogenic phages have been shown to carry genes
that can modify the Salmonella O antigen, which is one of the major antigens to which
the immune response is directed. Toxin production by Corynebacterium diphtheriae ismediated by a gene carried by a phage. Only those strains that have been converted by
lysogeny are pathogenic.
Plant Viruses
With plant viruses, the term specificity (or host-specificity) has a very narrow
meaning, since no plant virus as such exists. Instead, plant viruses can be grouped in anumber of varieties. The tobacco mosaic-virus (TMV), for example, multiplies withinNicotiana-species, several other solanaceous plants, and a few species of other plant
families.
The name of a virus is usually derived from the name of its main host plant. The
genetic information of plant viruses is either encoded by single-stranded RNA (most
plant viruses), double-stranded RNA (wound tumor viruses), single-stranded DNA(gemini-viruses) or double-stranded DNA (cauliflower mosaic-virus: CaMV).
Based on the shape of the virus particle, plant viruses can be distinguished as rod-
shaped and icosaedrical viruses with a capsid which is almost spherical.
TMV has helically arranged protein capsomers enclosingRNA. The RNA has a molecular weight of 2.1 x 106.
The protein coat consists of 2130 identical
polypeptide chains, each with a molecular weight of17.500. The polypeptide is made up of 158 amino
acid residues. The molecular weight of the TMV
virus particle (virion) is 40 x 106.
Structure of a tobacco mosaic-virus (TMV)
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Plant viruses have no specific mechanism for entering the host cell. Cell wall and
cuticle are difficult obstacles for them. Plant viruses depend therefore on injuries or ontransmission via invertebrates (insects, nematodes, etc.). The animal transmitter does in
some cases also act as an intermediate host. This means that some plant viruses are ableto multiply within animal tissue.
Viruses cause many important plant diseases and are responsible for huge lossesin crop production and quality in all parts of the world. Infected plants may show a range
of symptoms depending on the disease but often there is leaf yellowing (either of the
whole leaf or in a pattern of stripes or blotches), leaf distortion (e.g. curling) and/or other
growth distortions (e.g. stunting of the whole plant, abnormalities in flower or fruitformation).
Plant Viral Diseases
Virus diseases of plants are relatively rare. Infection is scarcely strong enough to
kill the plant. Monoculture favours spreading, and agricultural losses of profit.
Lettuce mosaic virus
LMV is a virus with flexuous filamentous particles approximately 750 x 13 nm. It
is sap-transmissible to a wide range of species, often seed-borne in lettuce and
transmitted by several aphid species in the non-persistent manner.
Grapevine fanleaf virus
This is an isometric virus particle with angular outline, about 30 nm in diameter,occurring worldwide in Vitis species. They are composed of a single protein of Mr
56,000. The virus causes fanleaf and yellow mosaic diseases of grapes. Fanleaf disease is
characterized by malformations of leaves (open marginal and petiolar sinuses, prominentmarginal teeth, asymmetrical blades, irregular veins).
Tomato Bushy Stunt Virus
TBSV is a soil-borne virus with isometric particles of about 30 nm diameter and
rounded outline found infecting economically important crops. Virus particles contain
one major linear positive sense, ssRNA species of c. 4.7 kb and a single coat protein ofMr 41,000. The virus is readily transmitted by mechanical inoculation to a wide range of
experimental hosts.
Natural transmission is through seed and soil, apparently without a vector. The
virus causes stunting and bushy growth, chlorotic spots, crinkling, deformation and
necrosis of leaves of tomato. Sometimes the virus is restricted to certain parts of the plant
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(e.g. the vascular system; discrete spots on the leaf) but in others it spreads throughout
the plant causing a systemic infection.
Infection does not always result in visible symptoms (as witnessed by names such
as Carnation latent virus and Lily symptom-less virus, both members of the genus
Carlavirus). Occasionally, virus infection can result in symptoms of ornamental value,such as breaking of tulips or variegation of Abutilon.
Spread of Plant Viruses
Since plant cells have a robust cell wall the viruses cannot penetrate them
unaided. Most plant viruses are therefore transmitted by a vector organism that feeds on
the plant or (in some diseases) are introduced through wounds made, for example, duringcultural operations (e.g. pruning). A small number of viruses can be transmitted through
pollen to the seed (e.g. Barley stripe mosaic virus, genus Hordeivirus) while many that
cause systemic infections accumulate in vegetatively propagated crops. The major
vectors of plant viruses are:
Insects: This forms the largest and most significant vector group and particularlyincludes:
Aphids: transmit viruses from many different genera, including Potyvirus,Cucumovirus and Luteovirus.
Whiteflies: transmit viruses from several genera but particularly those in thegenus Begomovirus.
Hoppers: transmit viruses from several genera, including those in the familiesRhabdoviridae and Reoviridae.
Thrips: transmit viruses in the genus Tospovirus. Beetles: transmit viruses from several genera, including Comovirus and
Sobemovirus
Control of Plant Viruses
Plant viruses cannot be directly controlled by chemical application. The major
means of control (depending on the disease) include:
Chemical or biological control of the vector (the organism transmitting thedisease, often an insect): this can be very effective where the vectors need to feed
for some time on a crop before the virus is transmitted but are of much less valuewhere transmission occurs very rapidly and may already have taken place before
the vector succumbs to the pesticide.
Growing resistant crop varieties: in some crops and for some viruses there arehighly effective sources of resistance that plant breeders have been using for
many years. However, no such natural resistance has been identified for manyothers.
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Transgenic resistance has shown considerable promise for many plant-viruscombinations following the discovery that the incorporation of part of the virus
genome into the host plant may confer a substantial degree of resistance.
Use of virus-free planting material: in vegetatively propagated crops (e.g.potatoes, many fruit crops) and where viruses are transmitted through seed major
efforts are made through breeding, certification schemes etc., to ensure that the
planting material is virus-free.
Exclusion: the prevention of disease establishment in areas where it does not yetoccur. This is a major objective of plant quarantine procedures throughout theworld as well as more local schemes.
Moreover, viroids were detected. Viroids are small, circular RNA molecules that
do not encode proteins themselves. Instead, virions interfere with the transcription ofcells due to their similarity with certain areas of recognition of primary transcription
products. It seems that viroids prevent the correct cutting out of the introns. They are
presumably multiplied with the aid of the cellular DNA-dependent RNA-polymerase II.Viroids occur mainly in warm climates and cause significant loss of profit as the
causative agents of the potato disease or the Cadang-Cadang disease of palms.
The virus concentration within plant cells is high, although a virus like the TMV
does not harm the host seriously. Infected cells contain often voluminous virus crystals.
Plants are far from being defenceless against viruses. Only a few virus species are
able to penetrate meristematic tissues or to infect a number of successive plantgenerations (vertical transmission). Hypersensitivity is an effective protection where viral
infection proceeds with dying of plant cells in the immediate surrounding of the primarysite of infection, thus stopping the spreading of the virus. The symptom a virus causes at
the primary site of infection is called primary symptom. Symptoms caused by its
spreading throughout the rest of the plant are called secondary symptoms.
Virus infections can usually be recognized by mosaic-like leaf patterns of lightand dark green. The infection spreads often over the whole leaf beginning at the leaf
veins. Leaves that had been infected during their development are usually deformed or
involute.
Frequently, lightened leaf areas, called chloroses, develop around the primary siteof infection. Withered areas are called necroses . Chloroses are caused by a breakdown of
the chlorophyll resulting in a decreased rate of photosynthesis. Heavy infections are
characterized by a complete local loss of chlorophyll. Affected areas have a yellowishlook as only the carotenoids remain. Some TMV strains, for example, can be recognized
by yellow leaf areas ("yellow strains").
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Some viruses multiply within the plant without causing symptoms. This
phenomenon is called latent infection. In contrast, wound tumor virus cause the
development of tumors. The symptoms of most viruses are dependent on both virus andhost, and do thus present an important diagnostic feature.
The TMV virus uses the plants vascular system for spreading. As a result, fullydifferentiated, old leaves and roots, and young leaves are equally infected. A number of
TMV wild types differing, for example, in their host range or in the primary structure oftheir coat proteins exist. The classic strain that at the same time is the one that proliferates
best on tobacco plants is called vulgare. A strain from tomatoes that proliferates equally
well on tobacco plants is called dahlemense. A third strain gained from plantain is knownas Holmes ribgrass.
Spherical (icosaedrical) Viruses
The densely packed nucleic acid of many spherical viruses is enclosed by a
protein coat also called capsid. The capsid is a polyhedral, i.e. it has many sides. Theexact number is specific for the respective species. The aggregated polypeptides form
morphological units often composed of several identical polypeptide chains. The crystal
structures of a number of different RNA-containing plant viruses are known, among them
are:
the tomato bushy stunt virus (TBSV),
the southern bean mosaic-virus (SBMV),
the satellite of the tobacco necrosis virus (STNV),
and the turnip crinkle-virus (TCV).
All of them have an icosaedrical structure. They consist of 60 (= 5 x 12) identicalpolypeptide copies of with the same building pattern assembled to form a hollow sphere.Simple examples of this type of architecture are the SBMV and the TBSV.
RNA-Viruses with Split Genomes
A number of RNA plant viruses contain more than just one molecule of RNA per
virion. In others, the genome is distributed among several virus particles.
The cucumber mosaic virus (CMV) is an example of the first type. It contains five
molecules of RNA, four of which are required for the replication of the virus, the fifth is
likely to have a helper function and can be classified as satellite-RNA (CARNA 5).
Incomplete viruses, satellite viruses: The multiplication of viruses leads often toincomplete infectious particles. They contain often cellular RNA instead of a complete or
partial viral-RNA. This frequently high proportion of non-infectious particles makes it
very difficult to determine the plating efficiency of the virus.
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The genome of the alfalfa mosaic virus (AMV) consists of three molecules of
RNA contained in three capsids (the B, M, and Tb-particle). All three particles together
are infectious, the RNA isolated from them alone is not infectious.
In satellite viruses, the infectiousness depends on the presence of a helper virus.
The tobacco-necrosis virus (TNV) and its satellite (STNV) are a typical example. Themultiplication of the TNV is not dependent on the presence of STNV. TNV alone
produces large lesions in tobacco plants. These lesions are small if STMV is present.
Double-Stranded RNA-Viruses; Wound Tumor Viruses
The genome of wound tumor viruses (WTV) consists of 12 double-stranded RNA
segments. Neither of them is infectious. The wound tumor viruses of plants and animals
(reoviruses) are related and are characterized by a number of common activities. Theycontain, for example, the enzyme transcriptase that transcribes single-stranded RNA or,
in other words, produces an mRNA complementary to the transcribed strand. Each of the
12 segments can be transcribed and it is assumed that each of them encodes one protein.Replication occurs within the cytoplasm. Infection takes place via insects (e.g. aphids)
that function both as a vector and an intermediate host, i.e. the virus multiplies in their
tissue, too.
More than 50 plant species are known to be susceptible for wound tumor viruses.Among the symptoms are small tumors at the stem and larger and more numerous ones at
the roots. WTV-induced wound tumors of leguminosae can be clearly distinguished from
the nodules caused by nodule bacteria. In some plant species, like the lobelia, the
infection induces the development of organs from otherwise normal organs, e.g. a leafcan develop at the lower leaf surface of another leaf.
Plant Viruses with Circular, Single-Stranded DNA: Gemini Viruses
The particles of gemini viruses are quasi-isometric. They are called gemini (twin)
viruses, because they are usually found in pairs. Each particle has a diameter of just 15 20 nm. Gemini viruses belong to the smallest virus particles able to multiply without a
helper virus. They have a circular DNA with a molecular weight of 0.7 0.8 x 106 (about
2,500 base pairs). In the case of some gemini viruses the genome consists of twomolecules of DNA of almost equal size, but different sequence.
Isolated circular DNA alone is not infectious. In infected host cells, the nucleus
holds the chief amount of viral DNA. It is therefore assumed that the nucleus is also theplace of its replication. It looks as if analogous to the TMV double-strandedintermediates would exist (= replication state: RF), since double-stranded DNA has been
isolated from infected cells. The bean golden mosaic-virus (BGMV), the cassava latend-
virus (CLV), the tomato golden-mosaic-virus (TGMV), the maize-streak virus (MSV),and the abutilon mosaic-virus belong all to the Gemini-virus family.
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Insects (greenhouse whitefly, grasshoppers, and others) help usually in spreading
Gemini-viruses in nature. These viruses can cause considerable damage to agriculture.
Double-Stranded DNA Viruses
The prototype of a plant virus with double-stranded DNA is the cauliflower
mosaic-virus (CaMV). CaMV-DNA is normally not incorporated constantly into the host
cell genome. CaMV is the collective name for a group of tightly related viral speciesusually transmitted by aphids. Each species has a narrow host specificity, overlapping
with that of other species is rare. The virion is spherical with a diameter of about 50 nm.
Most likely, the capsid consists of 420 identical subunits with molecular weights of
42,000. The DNA contains about 8,000 base pairs.
Symptoms occur two to three weeks after infection and can be recognized by the
mosaic-like lesions of infected leaves. The virus spreads systemically, its secondary
symptoms are similar to those of the primary infection. Leaves that were infected duringtheir development display deformed leaf blades.
Viroids
Viroids are infectious units that cause a number of plant diseases. They are
circular molecules of RNA. Ex: Potato spindle tuber virus (PSTV). It consists of 359
ribonucleotides and is characterized by numerous intramolecular base-pairings that lendstability to the structure. They are organized in a sequence of helices separated from each
other by loops. The resulting structure resembles a dumb-bell with an axis ratio of 1:20.
They are all single stranded covalent circles There is extensive intramolecular base pairing A DNA-directed RNA polymerase makes both plus and minus strands
Replication does not depend on the presence of a helper virus
No proteins are encoded
Several more viroids have been sequenced in the meantime. All of them havestructures similar to that of the PSTV. They are ~240 380 nucleotides long and all of
them have dumb-bell structures. The fact that a central portion of the molecule that is
responsible for the pathogenicity of the viroids, is structurally conserved is especiallyinteresting.
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Viroids multiply even at relatively high temperature (about 35C). Most likely,
they have adapted to their host plants that have so-far strictly been found to inhabit
tropical, subtropical, and continental climates. The viroids are localized within thechromatin fraction of the nucleus. The DNA-dependent RNA-polymerase II and I use the
viroids as templates and produce strands that again serve as templates for the synthesis of
the + strand.
Slow Viruses and DI Viruses
The plants infected with DNA viruses (other than the full length viral genomes),
often contain one or more types of smaller DNAs (subviral molecules) derived fromthem. These smaller versions of the viral DNAs accumulate to significant levels in the
infected tissues. In most cases they interfere with viral multiplication resulting in
symptom amelioration and hence, interference. In many cases, their interfering naturesare not well-established and are consequently called defective DNA or subgenomic DNA.
To undergo a complete infectious cycle such defective genomes need original/helper
virus to provide the missing functions, like replication and encapsidation.
Plant viruses with circular double-stranded DNA (dsDNA) which replicate by
reverse transcription through an RNA intermediate (caulimoviruses and badnaviruses),
and those with circular single-stranded DNA (ssDNA), which replicate through a dsDNAintermediate (the geminiviruses, nanoviruses and associated DNA satellites) by rolling
circle replication in the nuclei of infected cells and also by recombination-dependent
replication are occurring. Defective DNA molecules have been reported for both the
above types, which fall into three families, namely Geminiviridae,Nanoviridae andCaulimoviridae. In addition, geminivirus-associated satellite DNAs also give rise to
defective DNAs.
General Features of Animal Viruses
Animal viruses consist of nucleic acid (DNA or RNA) surrounded by a protein
coat called a capsid. The capsid is made up of individual structural subunits called
capsomeres. The combination of the nucleic acid genome enclosed in the capsid is called
the nucleocapsid. In addition, the animal viruses have an envelope, which is amembranous lipid structure that surrounds the nucleocapsid.
The structural components of a Herpes virus are illustrated below.
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Herpes simplex Virus 1, (HSV1) is an enveloped, icosahedral DNA virus. The regionbetween the outer lipid envelope and the nucleocapsid is called the tegument. The DNA
of the virus resides in the core. The envelope proteins ("Glycoprotein Spikes") are unique
viral proteins, but the envelope itself is derived from the virus host cell.
Classification of Animal Viruses
The primary criteria for taxonomic classification of animal viruses are based on
morphology (size, shape, etc.), type of nucleic acid (DNA, RNA, single-stranded,
double-stranded, linear, circular, segmented, etc.), and occurrence of envelopes. ssRNAviruses possess either (+)RNA (if it serves as messenger RNA) or (-)RNA (if it serves as
a template for messenger RNA). Host range is not a particularly reliable criterion forclassification. Although some animal viruses exhibit a very narrow or specific host range,
such as HIV in humans or canine distemper virus (CDV) in dogs. But for classification
purposes, host range cannot be a criterion because each animal species is subject toinfection by a wide variety of viral agents, and numerous viruses infect several different
animal species. West Nile virus, for example, has a primary host of birds, but it infects
and causes disease in horses and humans. Some viruses, such as the influenza virus, are
able to change their structure in such a way that they can shift from one primary host toanother, for example birds to humans.
Morphologic similarity among animal viruses correlates closely with similarity of
viral components, particularly with the type and size of the viral nucleic acid (genome).
For example, all viruses with the morphology of adenoviruses contain dsDNA genomeswith a molecular weight of about 23 million daltons; all reoviruses contain segmented
dsRNA genomes. In fact, a system of virus classification based on structure and size of
viral genomes yields that same grouping as one based on morphology.
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This information is organized in two ways.
According to the Baltimore method of classification, animal viruses are be
separated into several classes, grouped by type of nucleic acid. Class I. dsDNA viruses;
Class II. ssDNA viruses; Class III. dsRNA viruses; Class IV. (+)RNA viruses; Class V.
(-)RNA viruses: Class VI. RNA reverse transcribing viruses; Class VII. DNA reversetranscribing viruses.
The Baltimore method of classification
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On the basis of morphology alone, animal viruses are organized into a
hierarchical scheme consisting of virus families and constitutive genera based on size,
shape, type of nucleic acid and the presence or absence of an envelope. Some families ofviruses generated in this scheme are described and illustrated below.
Some families of Animal Viruses
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Replication of Animal Viruses
Outside its host cell a virus is an inert particle. However, when it encounters a
host cell it becomes a highly efficient replicating machine. After attachment and gaining
entry into its host cell, the virus subverts the biosynthetic and protein synthesizing
abilities of the cell in order to replicate the viral nucleic acid, make viral proteins andarrange its escape from the cell. The process occurs in several stages and differs in its
details among DNA-containing and RNA-containing viruses.
The Stages of Replication
1. The first stage in viral replication is called the attachment (adsorption) stage.
Animal viruses attach to host cells by means of a complementary association
between attachment sites on the surface of the virus and receptor sites on the host cell
surface. This accounts for specificity of viruses for their host cells. Attachment sites onthe viruses (called virus receptors) are distributed over the surface of the virus coat
(capsid) or envelope, and are usually in the form of glycoproteins or proteins. Receptorson the host cell (the host cell receptors) are generally glycoproteins imbedded into thecell membrane. Cells lacking receptors for a certain virus are resistant to it and cannot be
infected.
Attachment can be blocked by antibody molecules that bind to viral attachment
sites or to host cell receptors. Since antibodies block the initial attachment of viruses to
their host cells, the presence of these antibodies in the host organism are the mostimportant basis for immunization against viral infections.
2. The penetration stage follows attachment.
Penetration of the virus occurs either by engulfment of the whole virus, or byfusion of the viral envelope with the cell membrane allowing only the nucleocapsid of the
virus to enter the cell. Animal viruses generally do not "inject" their nucleic acid into host
cells as do bacteriophages, although occasionally non enveloped viruses leave theircapsid outside the cell while the genome passes into the cell.
3. Once the nucleocapsid gains entry into the host cell cytoplasm, the process of
uncoating occurs.
The viral nucleic acid is released from its coat. Uncoating processes are
apparently quite variable and only poorly understood. Most viruses enter the host cell in
an engulfment process called receptor mediated endocytosis and actually penetrate thecell contained in a membranous structure called an endosome. Acidification of the
endosome is known to cause rearrangements in the virus coat proteins which probably
allows extrusion of the viral core into the cytoplasm.
Some antiviral drugs such as amantadine exert their antiviral effect my preventing
uncoating of the viral nucleic acid.
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4. Immediately following uncoating, the viral synthesis stage begins.
Exactly how these events will unfold depends upon whether the infecting nucleic
acid is DNA or RNA.
In DNA viruses, such as Herpes, the viral DNA is released into the nucleus of the
host cell where it is transcribed into early mRNA for transport into the cytoplasm where
it is translated into early viral proteins. The early viral proteins are concerned withreplication od the viral DNA, so they are transported back into the nucleus where they
become involved in the synthesis of multiple copies of viral DNA. These copies of the
viral genome are then templates for transcription into late mRNAs which are alsotransported back into the cytoplasm for translation into late viral proteins. The late
proteins are structural proteins (coat envelope proteins) or core proteins (certain
enzymes) which are then transported back into the nucleus for the next stage of thereplication cycle.
In the case of some RNA viruses (picornaviruses), the viral genome (RNA) stays
in the cytoplasm where it mediates its own replication and translation into viral proteins.In other cases (orthomyxoviruses), the infectious viral RNA enters into the nucleus where
it is replicated before transport back to the cytoplasm for translation into viral proteins.
5. Once the synthesis of the various viral components is complete, the assembly stagebegins.
The capsomere proteins enclose the nucleic acid to form the viral nucleocapsid.
The process is called encapsidation. If the virus contains an envelope it will acquire thatenvelope and asssociated viral proteins in the next step.
6. The release stage is the final event in viral replication, and it results in the exit of themature virions from their host cell.
Virus maturation and release occurs over a considerable period of time. Some
viruses are released from the cell without cell death, by egestion, whereas others are
released when the cell dies and disintegrates. In the case of enveloped viruses, thenucleocapsid acquires its final envelope from the nuclear or cell membrane by a budding
off process (envelopment) before egress (exit) out of the host cell. Whenever a virus
acquires a membrane envelope, it always inserts specific viral proteins into the thatenvelope which become unique viral antigens and which will be used by the virus to gain
entry into a new host cell.
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Replication of enveloped double stranded DNA virus: Herpes simplex virus (HSV)
The replication cycle of Herpes Simplex virus
1. Specific proteins in the viral envelope attach to host cell receptors on the cellmembrane. 2. Penetration is achieved when the viral envelope fuses with the cell
membrane releasing the nucleocapsid directly into the cytoplasm. 3. The virion is
uncoated and the viral DNA is transported into the nucleus. 4. In the nucleus, the viral
DNA is transcribed into early mRNAs which are transported to the cytoplasm for thetranslation of early proteins. These early proteins are brought back into the nucleus and
participate in the replication of the virus DNA into many copies. The viral DNA is then
transcribed into the late mRNAs which exit to the cytoplasm for translation into the late
(nucleocapsid and envelope) proteins. 5. The capsid proteins encapsidate the newlyreplicated genomes. The envelope proteins are imbedded in the nuclear membrane. 6. The
nucleocapsids are enveloped by budding through the nuclear membrane, and the matureviruses are released from the cell through cytoplasmic channels.
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Replication of Influenza virus is an enveloped, single stranded (-)RNA virus that
contains a segmented genome:
The replication cycle of Influenza A Virus.
1. The virus adsorbs to the cell surface by means of specific receptors. 2. The virus is
taken up in a membrane enclosed endosome by the process of receptor mediatedendocytosis. 3. Uncoating takes place in the endosome and the viral RNA (genome) is
released into the cytoplasm. 4. The (-)RNA of the viral genome is transported into the
nucleus where it is replicated and copied by a viral enzyme into (+)RNA which is both
messenger RNA and serves as a template for more (-)RNA. The (+)RNA is transportedinto the cytoplasm for translation into early and late viral proteins. 5. The viral core
proteins are transported back into the nucleus to assemble as the capsid around the viral
(-) RNA forming the "ribonucleoprotein core" or the genome-containing nucleocapsid of
the virus. The viral envelope proteins assemble themselves in the cell membrane. 6. Thenucleocapsid recognizes specific points on cell membrane where viral proteins have
become inserted and buds off of the membrane to be released during enclosure in theviral envelope.
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How Viruses Cause Disease
There are several possible consequences to a cell that is infected by a virus, and
ultimately this may determine the pathology of a disease caused by the virus.
Lytic infections result in the destruction of the host cell. Lytic infections are
caused by virulent viruses, which inherently bring about the death of the cells that theyinfect.
When enveloped viruses are formed by budding, the release of the viral particles
may be slow and the host cell may not be lysed. Such infections may occur over
relatively long periods of time and are thus referred to as persistent infections.
Viruses may also cause latent infections. The effect of a latent infection is that
there is a delay between the infection by the virus and the appearance of symptoms. Feverblisters (cold sores) caused by herpes simplex type 1 result from a latent infection; they
appear sporadically as the virus emerges from latency, usually triggered by some sort ofstress in the host.
Some animal viruses have the potential to change a cell from a normal cell into a
tumor cell, the hallmark of which is to grow without restraint. This process is called
transformation. Viruses that are able to transform normal cells into tumor cells are
referred to as oncogenic viruses.
The vast majority of viral infections in humans are inapparent or asymptomatic.
Viral pathogenesis is the abnormal situation and it is of no particular value to the virus,although it typically results in the multiplication of the viruses that can be transmitted to
other individuals. For pathogenic viruses, there are a number of critical stages inreplication which determine the nature of the disease they produce.
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The possible effects that animal viruses may have on the cells that they infect.
The Stages of Viral Infections
1. Entry into the Host
The first stage in any virus infection, irrespective of whether the virus is pathogenic or
not. In the case of pathogenic infections, the site of entry can influence the disease
symptoms produced.
Infection can occur via several portals of entry:
Skin - Most viruses which infect via the skin require a breach in the physical integrity of
this effective barrier, (cuts or abrasions). Some viruses employ vectors (ticks, mosquitos)
to breach the skin.
Respiratory tract - The respiratory tract and all other mucosal surfaces possesssophisticated immune defense mechanisms, as well as non-specific inhibitory
mechanisms (ciliated epithelium, mucus secretion, lower temperature) which viruses
must overcome. This is the most common point of entry for most viral pathogens.
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Gastrointestinal tract - a fairly protected mucosal surface, but some viruses (e.g.
enteroviruses, including polioviruses) enter at this site.
Genitourinary tract - less protected than the GI tract, but less frequently exposed to
extraneous viruses.
Conjunctiva - an exposed site and relatively unprotected.
2. Primary Replication
Having gained entry to a potential host, the virus must initiate an infection by
entering a susceptible cell. Some viruses remain localized after primary infection, but
others replicate at a primary site before dissemination and spread to a secondary site.
Examples are given in the table below.
Localized Infections:
Virus: Primary Replication:Rhinoviruses Upper respiratory tract
Rotaviruses Intestinal epithelium
Papillomaviruses Epidermis
Systemic Infections:
Virus: Primary
Replication:
Secondary Replication:
Enteroviruses
(poliovirus)
Intestinal epithelium Lymphoid tissues, CNS
Herpesvirus (HSV
types 1 and 2)
Oropharynx or
urogenital tract
Lymphoid cells, peripheral
nervous system, CNS
Rabies virus Muscle cells andconnective tissue
CNS
3. Dissemination Stage
There are two main mechanisms for viral spread throughout the host: via the
bloodstream and via the nervous system.
The virus may get into the bloodstream by direct inoculation - arthropod vectors, blood transfusion or I.V. drug abuse. The virus may travel free in the plasma
(Togaviruses, Enteroviruses), or in association with red cells (Orbiviruses), platelets
(HSV), lymphocytes (EBV, CMV) or monocytes (Lentiviruses). The presence of virusesin the bloodstream is referred to as a viremia. Primary viremia may be followed by
more generalized secondary viremia as the virus reaches other target tissues or replicates
directly in blood cells.
In some cases, spread to nervous system is preceded by primary viremia, as
above. In other cases, spread occurs directly by contact with neurons at the primary siteof infection. Once in peripheral nerves, the virus can spread to the CNS by axonal
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transport along neurons (HSV). Viruses can cross synaptic junctions since these
frequently contain virus receptors, allowing the virus to jump from one cell to another.
4. Tissue/Cell tropism
Tropism is the ability of a virus to replicate in particular cells or tissues. It is
influenced partly by the route of infection but largely by the interaction of a virus
attachment sites (virus receptors) with specific receptors on the surface of a cell. Theinteraction of the virus receptors with the host cell receptors may have a considerable
effect on pathogenesis.
5. Host Immune Responses
There are several ways that the host immune responses may contribute to viral
pathology. The mechanisms of cell mediated immunity are designed to kill cells which
are infected with viruses. If the mechanisms of antibody mediated immunity result in theproduction of antibodies that cross-react with tissues, an autoimmune pathology may
result.
6. Secondary Replication
This occurs in systemic infections when a virus reaches other tissues in which it iscapable of replication. For example, polioviruses initiate infection in the GI where the
produce an asymptomatic infection. However, when disseminated to neurons in the brain
and spinal cord, where the virus replicates secondarily, the serious paralytic complicationof poliomyelitis occurs. If a virus can be prevented from reaching tissues where
secondary replication can occur, generally no disease results.
7. Direct Cell and Tissue Damage
Viruses may replicate widely throughout the body without any disease symptoms
if they do not cause significant cell damage or death. Although retroviruses (e.g. HIV) do
not generally cause cell death, being released from the cell by budding rather than by celllysis, they cause persistent infections and may be passed vertically to offspring if they
infect the germ line. Conversely, most other viruses, referred to as virulent viruses,
ultimately damage or kill their host cell by several mechanisms, including inhibition ofsynthesis of host cell macromolecules, damage to cell lysosomes, alterations of the cell
membrane, development of inclusion bodies, and induction of chromosomal aberrations.
8. Persistence versus Clearance
The eventual outcome of any virus infection depends on a balance between the
ability of the virus to persist or remain latent (persistence) and the forces of the host to
completely eliminate the virus (clearance).
Long term persistence is the continued survival of a critical number of virus
infected cells sufficient to continue the infection without killing the host. It results fromtwo main mechanisms:
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a. Regulation of lytic potential. For viruses that do not kill their host cells, this is not
usually a problem. But for lytic (virulent) viruses, there may be ways to down
regulate their replicative and lytic potential so that they can persist in a state oflatency without replication and damage to their host cell. This is the case with herpes
viruses.
b. Evasion of immune surveillance.
This may be due to several conditions that are properties of the host or the virus.
Some viruses, such as influenza, can undergo antigenic shifts or antigenic drift that
allows them to bypass a host immune response. Some viruses, e.g., measles, may inducea form of immune tolerance such that the host is unable to undergo an effective immune
response to the virus. Other viruses, such as HIV, may set up a direct attack against cells
of the immune system such that the immune system is compromised in its ability toattack or eliminate the virus.
List of important virus families that contain genera that infect humans and the
symptoms that they cause
DNA- containing viruses
AdenoviridaeHuman Adenoviruses - primarily respiratory and conjunctival infections
Astroviridae
Astrovirus - flulike symptoms
Herpesviridae
Herpes simplex virus type 1 - stomatitis; upper respiratory infectionsHerpes simplex virus type 2 - genital infections
Varicella-zoster - chicken pox; herpes zoster; shingles ,
Human Cyotmegalovirus - jaundice; hepatosplenomegaly, brain damage, deathEpstein-Barr Virus - Burkitt's lymphoma; nasopharyngeal carcinoma; infectious
mononucleosis
PapovaviridaeHuman papilloma viruses- benign tumors (warts); cervical cancer
Human polyoma viruses - progressive leukoencephalopathy (PML); transform cells
in tissue culture
Poxviridae
OrthopoxvirusVariola - smallpox
Cowpox - vesicular lesions on skin
Unclassified Round-structured viruses
Norwalk agent "Noroviruses" - gastroenteritis
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RNA - containing viruses
Arenaviridae
Lymphocytic choriomeningitis virus (LCM) - fatal meningitisLassa virus - hemorrhagic fever, frequently fatal
BunyaviridaeHanta virus
Coronaviridae
Human Coronavirus - SARS - severe acute respiratory syndrome
Filoviridae
Ebola - acute hemorrhagic fever almost 90% case mortality
Marburg - hemorrhagic fever, frequently fatal
FlaviviridaeYellow Fever - hemorrhagic fever, hepatitis, nephritis
Dengue - fever, arthralgia, rash
West Nile - fever, arthralgia, rash
Hepatitis C virus - hepatitis
Orthomyxoviridae
Influenza virus type A - acute respiratory diseaseInfluenza virus type B - acute respiratory disease
Influenza virus type C - acute respiratory disease
Paramyxoviridae
Parainfluenza viruses - croup, common cold syndrome, mild respiratory disease
Mumps - parotitis, orchitis, meningoencephalitisMeasles - measles
Subacute sclerosing panencephalitis (SSPE) - chronic degeneration of CNS
Respiratory syncytial virus (RSV) - pneumonia and bronchiolitis in infants and
children, common cold syndrome
Picornaviridae
Human EnterovirusesPoliovirus - poliomyelitis
Coxsackie virus A - aseptic meningitis, paralysis, and common cold syndrome
Coxsackie virus B - aseptic meningitis, paralysis, severe systemic illness ofnewborns
Hepatitis A virus - infectious hepatitis
Human Rhinoviruses - common cold, bronchitis, croup, bronchopneumonia
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Reoviridae
Colorado Tick fever virus - encephalitis
Human Rotaviruses - diarrhea in infants
Retroviridae (RNA-tumor viruses)
Human immunodeficiency virus - acquired immune deficiency syndrome (AIDS)Human T-lymphotrophic virus (HTLV)
RhabdoviridaeRabies virus - encephalitis, usually fatal
Togaviridae
Eastern Equine Encephalitis virus - encephalitisWestern Equine Encephalitis virus - encephalitis
Rubella (Measles) - severe deformities of fetuses in first trimester of pregnancy
Cultivation and enumeration of viruses
Laboratory animals
The laboratory animals are considered equivalent animal models of human
infection. Historically the only way to study viruses was from animal to animal. But thismethod of analysis faced several problems: 1) They are inconvenient and expensive, 2)
not defined system- leads to generation of virus mutants, 3) animal welfare issues.
However, these methods have advantages like some viruses can only be studied andmethod gives unique insight into virus pathogenesis.
Embryonated eggs have been used as alternative models.
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Cell culture
This method is currently the most common way to study the viruses. Sterility isan important aspect in employing them. The cells can be infected synchronously to obtain
viruses on large scale.
The different types of cells employed for virus infection are:
Primary cells- These are derived directly from animal tissue. Ex: Chick embryo,human foreskin, monkey kidney, etc.
Diploid cell lines- These cells maintain the diploid number of chromosomes but
can divide up to 100 times. Ex: usually cells from human embryos
Continuous cell lines- Such cells can be propagated indefinitely. They are
derived usually from a tumor tissue or by treating primary or diploid cells with mutagens
or tumor viruses. These cells have little resemblance to original cell and posses abnormalchromosome numbers (aneupoloid), and can be tumorigenic. Ex: HeLa, Vero, L929,
CHO, etc.
Also the diploid and continuous cells can be frozen in liquid nitrogen for later use.
The different cell types can be cultured in the laboratory as monolayer cells orsuspension cells. The monolayer cells can be obtained on a solid surface like plastic orglass. Where as if cells are required on a large scale, the cells can be cultured (spinner
culture) as suspension cell cultures.
In any case the culture of cells in laboratory requires the supply of food in the
form of chemically defined media. The designed medium is an isotonic solution of salts,glucose, vitamins, coenzymes, amino acids, buffered to 7.3 (with CO2) and antibiotics.
An important constituent of cell culture medium is the serum, it provides the growth
factors required for the cells to grow in culture. On cell culturing most cell lines doubleevery 24-48 hours and must be passaged(divided) into new cultures every 3-4 days. The
adherent monolayers of cells are removed from the containers by treating with trypsin
(proteolytic enzyme) and versene (EDTA).
The viral infection of cell cultures generates typical cytophathic effects (CPE).
Some viruses kill the cells in which they replicate. Such an incident is often easily visible
as CPE in some viral infections, but other viral infections do not show any visible CPE.The other type of CPE is in the form of typical rounding or detaching of cells and cell
fusion called syncytia. Thus cytophatic effects due to viral infections of animal cells vary
from virus to virus and they can be diagnostic in nature.
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Table. 9. Some cytophathic effects
Detection and quantification of infectious viruses
Here the amount of virus that causes infection in the system is detected. The
measure of virus is referred to as titer. Thus virus titer is a measure of the concentration
of the virus. The virus titer can be determined by several methods: Plaque assay,fluorescent focus assay, infectious center assay, transformation assay, endpoint dilution
assay, etc. The virus titers can be as high as 1010 infections/ml, or very low.
The plaque assay
The monolayers of cells are exposed to a defined dilution of virus, such that the
virus is adsorbed. The inoculum is removed and the cells covered with medium that
includes a gelling substance like agar. The gel prevents long range spread of virus but
allows virus to infect neighboring cells- thus causing a localized infection. With time theplaques become visible with naked eye, or can be seen after staining the cells (with neural
red, crystal violet). A plaque assay will work with viruses that cause CPE. Thevisualization can be improved with histochemical stains. The viral titer is usuallyexpressed as plaque forming units (PFU).
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Make serial dilutions of virus
Plate dilutions onto susceptible cells, after
virus attachment, overlay cells with
semisolid medium which restricts
diffusion of viral particles
Restricted cell-to-cell spread of virusresults in localized destruction of cell
monolayer visible as plaques.
Fluorescent focus assay
Infection is scored by addition of virus-specific antibody, and fluorescent
secondary antibody and visualization under the microscope usually after a single round of
infection. The infectivity can be scored as FFU/cell. This assay is not accurate but usefulin some respects.
Infectious Center Assay
This a modification of the plaque assay where infected cells are mixed with non-
infected cells before plating. This method is useful for persistently infected cells.
Transformation assay
It is considered as inverse plaque assay. It measures the production of foci oftransformed cells (small piles). The measureme