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Orthomyxoviruses

Orthomyxoviruses. 80-120 nm, spherical ssRNA, negative sense Segmented (8) genome. Gen products:. PB2: RNA polymerase; recognise the cap PB1-F2: Propaoptotic activity PB1: RNA pol., endonuclease, elongation PA: RNA pol.; protease HA: Surface GP, receptor binding, fusion; major antigen

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Orthomyxoviruses

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  1. Orthomyxoviruses 80-120 nm, spherical ssRNA, negative sense Segmented (8) genome

  2. Gen products: • PB2: RNA polymerase; recognise the cap • PB1-F2: Propaoptotic activity • PB1: RNA pol., endonuclease, elongation • PA: RNA pol.; protease • HA: Surface GP, receptor binding, fusion; major antigen • NP: RNA binding, RNA synthesis, transport of RNA to nucleus • NA: Surface GP; neuraminidase activity • M1: MAtrix protein; export from nucleus; interaction with vRNP surface glycoproteins; budding • M2: Membrane protein; ion channel activity; assembly • NS1: Multifunctional protein; agonist of viral IFN • NEP/NS2: Transport of vRNP from nucleus

  3. M1, M2 and NP are typespecific  İnfluenza A, B, and C

  4. Strains of influenza A virus are classified by the following four characteristics: • Type (A, B, and C) • Place of original isolation • Date of original isolation • Antigen (HA and NA) Influenza A/New York/07/09 (H1N1)

  5. Mutations in HA and NA genes  Antigenic drift • Reassorments  Antigenic shift

  6. Incidence of clinically manifest influenza Mean level of population antibody vs A HxNx Mean level of population antibody vs A HyNy Pandemic Pandemic Interpandemic Period Epidemic Epidemic Disease Incidence Mean Population Antibody Level Epidemic 1 2 3 4 5 6 7 8 9 10 11 12 Time in Years Introduction of hypothetical A HxNx virus Significant minor variation A HxNx may occur at any of these points. Epidemics may or may not be associated with such variations Introduction of hypothetical A HyNy major (new subtype) variant A HxNx disappears Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases, 5th ed. 2000:1829. Modified from Kilbourne ED. Influenza. 1987:274, with permission.

  7. Dünya Sağlık Örgütü Pandemi Uyarısı

  8. Epithelial demage () Viral shedding 5 -10 days No viremia Onset of the symptoms (1-5 days) Acute influenzaSymptoms regress (~ 5 day) Sekonder Bakteriyel Pnömoni/Komplikasyonlar Viral Pneumonia

  9. Common Diagnostic tests Rapid Antigen (EIA) Sensitivity: 60-80% Specificity: 90% Culture (Shell Vial) Sensitivity: 70-80% Specificity: 100% RT-PCR, multiplex RT, multiplex PCR, array, luminex based DFA

  10. PARAMYXOVIRUSES

  11. 15 kb lineer, negative sense RNA Speherical to plemorphic r > 150 nm 6 structutal proteins

  12. Unique Features of the Paramyxoviridae • Large virion consists of a negative RNA genome in a helical nucleocapsid surrounded by an envelope containing a viral attachment protein (hemagglutinin-neuraminidase [HN], parainfluenza virus and mumps virus; hemagglutinin [H], measles virus; and glycoprotein [G], respiratory syncytial virus [RSV]) and a fusion glycoprotein (F). • The three genera can be distinguished by the activities of the viral attachment protein: HN of parainfluenza virus and mumps virus has hemagglutinin and neuraminidase, and H of measles virus has hemagglutinin activity, but G of RSV lacks these activities.

  13. Virus replicates in the cytoplasm. • Virions penetrate the cell by fusion with the plasma membrane and exit by budding from the plasma membrane. • Viruses induce cell-cell fusion, causing multinucleated giant cells. • Paramyxoviridae are transmitted in respiratory droplets and initiate infection in the respiratory tract. • Cell-mediated immunity causes many of the symptoms but is essential for control of the infection.

  14. Measles virus

  15. Parainfluenzaviruses

  16. ♦ PIV types 1 and 2 most often cause outbreaks of croup in autumn/early winter, with an alternate year pattern. PIV-1 tends to attack children ages 2-6 years. • ♦ PIV-3 causes croup less commonly than PIV-1 and 2. Infections are sporadic and year-round, including spring and summer. Primary infection with PIV 3 in young infants and children <2 years of age is a fairly common cause of bronchiolitis and pneumonia. • ♦ PIV-4 infections, even primary infections, are usually milder and are generally associated with mild URI symptoms. • ♦ Particularly severe and persistent infections are known to occur in immunocompromised children and adults; prolonged viral shedding is seen.

  17. Mumps virus

  18. Respiratory syncytial virus • RSV A • RSV B • November-May epidemics

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