RESPIRATORY VIRUSES
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Transcript of RESPIRATORY VIRUSES
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RESPIRATORY VIRUSES
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Including…
• Orthomyxoviridae( 正粘病毒科 ) : Influenza virus• Paramyxoviridae( 副粘病毒科 ): Respiratory syncytial virus(RSV),measles virus, m
umps virus.• Other viruses rhinovirus,adenovirus,coronavirus…
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INFLUENZA VIRUS• RNA virus, genome consists of 8 seg
ments• enveloped virus, with haemagglutinin
and neuraminidase spikes• 3 types: A, B, and C• Type A undergoes antigenic shift and
drift.• Type B undergoes antigenic drift onl
y and type C is relatively stable
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Biological Properties
Segment Protein Function
1 PB2 Polymerase component
2 PB1 Polymerase component
3 PA Polymerase component
4 HA Hemagglutinin, viral attachment protein, fusion protein, target of neutralizing antibody
5 NP Nucleocapsid
6 NA Neuraminidase (cleaves sialic acid and promotes virus release)
7 M1 Matrix protein:Viral structural protein (interacts with nucleocapsid and envelope, promotes assembly)
M2 Membrane protein (forms membrane channel and target for amantadine facilitates uncoating and HA production)
8 NS1 Nonstructural protein (inhibits cellular mRNA translation)
NS2 Nonstructural protein (important but unknown function)
Structure and Composition
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HA
NA
PB2PB1PA
NP
RNA
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Antigen Soluble antigens: include ribonucleoprotein and M p
rotein which are much stable in antigenicity. Influenza viruses are divided into 3 groups determined by the ribonucleoprotein (RNP) antigen and M antigen: • Group A - This group is the cause of epidemics and pandemics and has an avian intermediate host (IH)• Group B - This group causes epidemics and has no IH• Group C - This group does not cause epidemics and causes mild disease• Surface antigens: include HA and NA which are mu
ch variable in antigenicity. According to antigenicity of HA and NA, influenza
virus is divided into subtypes such as HnNm( H1N2, et al )
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TYPE A
++++yesyesyesshift, driftyessensitivesensitive2
severity of illnessanimal reservoirhuman pandemicshuman epidemicsantigenic changessegmented genomeamantadine, rimantidinezanamivirsurface glycoproteins
TYPE B
++nonoyesdriftyesno effectsensitive2
TYPE C
+nonono (sporadic)driftyesno effect
(1)
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Epidemic
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Pathogenesis and Immunity
• Influenza virus spread rapid via aerial droplets and fomites with inhalation into the pharynx or lower respiratory tract.
• fever, myalgia, headache, pharyngitis, cough and prostration
• cell-mediated immune response is important, IgG and IgA are important in protection against reinfection
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where do “new” HA and NA come from?
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why do we not have influenza B pandemics?
• so far no shifts have been recorded
• no animal reservoir known
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Laboratory Diagnosis • Detection of Antigen - a hemagglutination inhibition
serologic test and ELISA.
• Virus Isolation - virus may be readily isolated from nasopharyngeal aspirates and throat swabs. The virus is generally isolated in primary monkey kidney cell cultures, the Madin-Darby canine kidney cell line, or embryonated eggs.
• Identify the influenza genome - RT-PCR
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Treatment and Prevention
• prevented by active immunization with a polyvalent killed or subunit vaccine
• Amantadine, Zanamivir and oseltamivir
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PARAMYXOVIRUSES • Paramyxoviruses are spherical,
enveloped viruses with a single helical nucleocapsid containing single-stranded, negative-sense RNA.
• a fusion (F) protein and a viral attachment protein (hemagglutinin-neuraminidase [HN], hemagglutinin [H], or G protein).
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Important properties of paramyxoviruses.
• Virion: Spherical, pleomorphic, 150 nm or more in diameter (helical nucleocapsid, 13–18 nm)
• Composition: RNA (1%), protein (73%), lipid (20%),carbohydrate (6%)
• Genome: Single-stranded RNA, linear, nonsegmented, negative-sense, noninfectious, about 15 kb
• Proteins: Six to eight structural proteins• Envelope: Contains viral hemagglutinin (HN) glycoprotei
n (which sometimes carries neuraminidase activity) and fusion (F) glycoprotein; very fragile
• Replication: Cytoplasm; particles bud from plasma membrane
• Outstanding characteristics: Antigenically stable/ Particles are labile yet highly infectious
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Characteristics of genera in the subfamilies of the family Paramyxoviridae.
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Measles virus
• Highly contagious, only one serotype and infects only humans
• The prodrome starts with high fever, cough, coryza, conjunctivitis and photophobia
• Typical mucous membrane lesions-Koplik's spots
• Exanthema of measles spreads over the body
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MEASLES - Koplik’s spots
Murray et al. Medical Microbiology
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MEASLES - RASH
CDC - B.Rice Murray et al. Medical Microbiology
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DISEASE• FEVER• RESPIRATORY TRACT SYMPTOMS
• rhinorrhea, cough
• KOPLIK’S SPOTS• MACULOPAPULAR RASH
• T-cells ->endothelial cells
• CONJUNCTIVITIS• epithelial cells
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MEASLES GIANT CELL PNEUMONIA
Murray et al. Medical Microbiology
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Measles virus• complication : pneumonia, encephalomyelitis, Subacute
sclerosing panencephalitis (SSPE)
• prevented by a live attenuated measles vaccine to children; immune globulin to exposed susceptible people
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Natural history of measles
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Mumps virus(腮腺炎病毒)
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Mumps virus
• cause of acute, benign viral parotitis 耳下腺炎 - a very communicable disease with only one serotype, and it infects only humans.
• spread by direct person-to-person • incubation period may range from 7 days to 25 days but is
typically about 18 days • may affect the testes and ovaries, causing swelling and
pain especially after puberty. Orchitis can result in sterility. • immunity is permanent • prevented by a live attenuated vaccine (MMR)
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Mims et al., Medical Microbiology 1993
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Parainfluenza virus • Types 1, 2, and 3 cause of severe lower respiratory t
ract infection in infants and young children. Type 4 causes only mild upper respiratory tract infection in children and adults
• transmitted by person-to-person
• Primary infections usually occur in infants and children younger than 5 years
• reinfections occur throughout life, indicating that immunity is short-lived
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Respiratory syncytial virus (RSV)
• no haemagglutinin or neuraminidase or hemolytic properties
• induces many large syncytia with cytoplasmic inclusions
• cause any respiratory tract illness, from a common cold to pneumonia
• pathologic effect-due to direct viral invasion of the respiratory epithelium, which is followed by immunologically mediated cell injury.
• No vaccine is currently available for RSV prophylaxis.
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Human metapneumovirus
• Newly isolation: 2001.• Respiratory infections.• Failed to grow on cell culture.• RT-PCR
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Nipah virus & Hendra virus
• Genus:Henipavirus 2002• Isolation:1999. zoonotic virus.• 120-500nm,not segmented,6 structural genes.• Natural host: 马来大狐蝠• It has caused disease in animals and in humans, through
contact with infectious animals. • Fever , headache , encephalitis…• High mortality rate.
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RUBELLA VIRUS • a member of the Togaviridae family • It cause German measles, a systemic infection characterized by
lymphadenopathy and morbilliform rash • transmitted via respiratory droplets and from mother to fetus
transplacentally • congenital rubella syndrome (CRS), cataracts, heart defects, sensorine
ural deafness, mental retardation• lifelong immunity • No treatment has been found for rubella • The best means of preventing rubella is vaccination with the live
attenuated vaccine
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Natural history of primary rubella infection:virus production and antibody responses.
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Adenovirus
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ADENOVIRUS
• 100 serotypes, at least 51 of which infect humans, classified into six species
• nonenveloped with an icosahedral nucleocapsid comprises 240 capsomeres, which consist of hexons and pentons
• spread by droplet, fomites and ingestion • causing lytic (e.g. muco-epithelial cells), latent (e.g. lymph
oid and adenoid cells), and transforming (hamster, not human)
• respiratory tract infection, conjunctivitis (pink eye), hemorrhagic cystitis, and gastroenteritis
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Disease At RiskAcute Respiratory Illness Military recruits, boarding schools,
Pharyngitis Infants
Gastroenteritis Infants
Conjunctivitis All
Pneumonia Infants, military recruits
Keratoconjunctivitis All
Acute Haemorrhagic Cystitis Infants
Hepatitis Infants, liver transplant
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swimming pool conjunctivitis
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CORONAVIRUS • Enveloped, pleomorphic morphology• 2 serogroups: OC43 and 229E• In March 2003, a novel coronavirus (SAR
S-CoV) was discovered in association with the outbreak of severe acute respiratory syndrome (SARS)
• SARS is a form of atypical pnermonia characterized by high fever (>38C), chills, rigors, headache, dizziness, malaise, and myalgia, cough or breathing difficulty, and a history of exposure to a person or place associated with SARS within the previous 10 days
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RHINOVIRUS
• belonging to the family Picornaviridae, more than 100 serotypes
• cause of the common cold and upper respiratory tract infections
• infections are self-limited and do not cause serious disease
• transmitted by two mechanisms, as aerosols and on fomites (e.g. by hands or on contaminated inanimate objects
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