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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 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 Unique Features of the Influenza A and B Viruses Enveloped virion has a genome of eight unique negative-sense RNA nucleocapsid segments. •Hemagglutinin glycoprotein is the viral attachment protein and fusion protein; it elicits neutralizing, protective antibody responses. •Influenza transcribes and replicates its genome in the target cell nucleus but assembles and buds from the plasma membrane. Body_ID: B059001 The antiviral drugs amantadine and rimantadine inhibit an uncoating step and target the M2 (membrane) protein for influenza A only. •The antiviral drugs zanamivir and oseltamivir inhibit the NA protein of influenza A and B. •The segmented genome promotes genetic diversity caused by mutation and reassortment of segments on infection with two different strains. •Influenza A infects humans, mammals, and birds (zoonosis). M1, M2 and NP are typespecific İnfluenza A, B, and C 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) Mutations in HA and NA genes Antigenic drift Reassorments Antigenic shift Pandemic DAte Pandemic Severity Index Deaths Subtype Asiatic 1889–1890 (Russian) Flu 1 million posible H2N2 ? Spanish Flu 1918–1920 40 to 100 million H1N1 5 Asian Flu 1957–1958 1 to 1.5 million H2N2 2 Hong Kong Flu 1968–1969 0.75 to 1 million H3N2 2 Swine flu 2009-2010 H1N1 Disease Incidence Pandemic Pandemic Interpandemic Period Epidemic Epidemic Epidemic 1 2 3 4 5 6 7 8 Time in Years 9 10 11 12 Mean Population Antibody Level Incidence of clinically manifest influenza Mean level of population antibody vs A HxNx Mean level of population antibody vs A HyNy Introduction of Significant minor variation A HxNx may Introduction of hypothetical hypothetical occur at any of these points. Epidemics A HyNy major (new subtype) A HxNx virus may or may not be variant A HxNx disappears associated with such variations Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases, 5th ed. 2000:1829. Modified from Kilbourne ED. Influenza. 1987:274, with permission. Dünya Sağlık Örgütü Pandemi Uyarısı Epithelial demage () No viremia Acute influenza Symptoms regress (~ 5 day) Onset of the symptoms (1-5 days) Viral Pneumonia Viral shedding 5 -10 days Sekonder Bakteriyel Pnömoni/Komplikasyonlar 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 PARAMYXOVIRUSES 15 kb lineer, negative sense RNA Speherical to plemorphic r > 150 nm 6 structutal proteins 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 (hemagglutininneuraminidase [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. 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. Measles virus Parainfluenzaviruses ♦ 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. Mumps virus Respiratory syncytial virus RSV A RSV B November-May epidemics Metapneumovirus First described in 2001 Widespread; seropositivity among young adults and older people 100% Smilar disaese as RSV Between Decembre and April Among young children less common compared to RSV Henipaviruses Hendra and Nipah viruses Zoonotic viruses (fruit bats) Endemic – Australasia Nipah virus Malaysia encephalitis (from pigs) Hendra Australia (equine virus) Togaviridae and Flaviviridae Rubella Togaviridae Rubivirus Positive sense SS RNA 70 nm 9 genotypes Incubation period: 12 days and longer Viremia: Devopes after 7-9 days and lasts till appearence of rush but viral shedding continues 20-50% subclinical Rush facetrunkextremities < 3 days In adults (esp. Women transient arthralgia) Rarely thrombocytopenic pupura and encephlaitis Epidemics every 6-10 years Explosive epidemics every 20-25 years In first semester 85% In second semester 15% Intrauterine infection viral persistance positive-strand RNA 27–33 kb 3′ structural proteins, including spike (S), envelope (E), membrane (M) and nucleocapsid (N) NS: replicase protein (ORF1 and 2) Human Coronavirus Group 1: Transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PDEV), feline infectious peritonitis virus (FIPV), canine coronavirus and HCoV-229E, HCoV-NL63 Group 2: Mouse hepatitis virus (MHV), bovine coronavirus, haemagglutinating encephalomyelitis virus, HCoV-HKU1 and HCoV-OC43; bat SARSCoV and SARS-CoV considered distantly related Group 2b coronaviruses. Group 3: Avian coronaviruses