RESPIRATORY VIRUSES

1. RESPIRATORY VIRUSES

3. Including… • Orthomyxoviridae(正粘病毒科) : Influenza virus • Paramyxoviridae(副粘病毒科): Respiratory syncytial virus(RSV),measles virus, mumps virus. • Other viruses rhinovirus,adenovirus,coronavirus…

4. INFLUENZA VIRUS • RNA virus, genome consists of 8 segments • 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 only and type C is relatively stable

5. Biological Properties Structure and Composition

6. HA NA RNA PB2 PB1 PA NP

7. Antigen • Soluble antigens: include ribonucleoprotein and M protein which are much stable in antigenicity. • Influenza viruses are divided into 3 groups determined by the ribonucleoprotein (RNP) antigen andM 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 much variable in antigenicity. According to antigenicity of HA and NA, influenza virus is divided into subtypes such as HnNm( H1N2, et al )

8. severity of illness animal reservoir human pandemics human epidemics antigenic changes segmented genome amantadine, rimantidine zanamivir surface glycoproteins TYPE A ++++ yes yes yes shift, drift yes sensitive sensitive 2 TYPE B ++ no no yes drift yes no effect sensitive 2 TYPE C + no no no (sporadic) drift yes no effect (1)

11. Epidemic

12. 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

14. where do “new” HA and NA come from?

15. why do we not have influenza B pandemics? • so far no shifts have been recorded • no animal reservoir known

16. 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

17. Treatment and Prevention • prevented by active immunization with a polyvalent killed or subunit vaccine • Amantadine, Zanamivir and oseltamivir

19. 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).

21. 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) glycoprotein (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

22. Characteristics of genera in the subfamilies of the family Paramyxoviridae.

23. 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

25. Measles virus • complication : pneumonia, encephalomyelitis, Subacute sclerosing panencephalitis (SSPE) • prevented by a live attenuated measles vaccine to children; immune globulin to exposed susceptible people

26. Natural history of measles

27. Mumps virus（腮腺炎病毒）

28. 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)

29. Mims et al., Medical Microbiology 1993

30. Parainfluenza virus • Types 1, 2, and 3 cause of severe lower respiratory tract 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

31. 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.

32. Human metapneumovirus • Newly isolation: 2001. • Respiratory infections. • Failed to grow on cell culture. • RT-PCR

33. Nipah virus & Hendra virus • Genus:Henipavirus2002 • 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.

35. RUBELLA VIRUS • a member of the Togaviridae family • It cause German measles, a systemic infection characterized by lymphadenopathyand morbilliform rash • transmitted via respiratory droplets and from mother to fetus transplacentally • congenital rubella syndrome (CRS),cataracts, heart defects, sensorineural 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

37. Natural history of primary rubella infection:virus production and antibody responses.

38. Adenovirus

39. 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. lymphoid and adenoid cells), and transforming (hamster, not human) • respiratory tract infection, conjunctivitis (pink eye), hemorrhagic cystitis, and gastroenteritis

41. swimming pool conjunctivitis

42. CORONAVIRUS • Enveloped, pleomorphic morphology • 2 serogroups: OC43 and 229E • In March 2003, a novel coronavirus (SARS-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 (>38C), 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

45. 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