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1 Orthomyxovirus Hugh B. Fackrell [email protected] Filename: orthomyx.ppt 5/13/2017 2 Orthomyxovirus Outline Structure Classification Multiplication Clinical manifestations Epidemiology Diagnosis Control Baron’s Web Site 5/13/2017 3 Structure Influenza viruses ssRNA, antisense, multipartite genome, 7-8 segments, 10 genes spherical OR filamentous enveloped hemagglutinin neuraminidase 5/13/2017 4 Flu Hemagglutinin Protein in viral envelope 13 different hemagglutinin antigens binds to N-aceytlneuraminic acid on host cell glycolipids or glycoproteins Hemagglutinin hydrolysed by host cell proteases to create infectious virion 5/13/2017 5 Flu Neuraminidase Found in the viral envelope 9 different neuraminidase antigens Removes N-acetylneuraminic acid from glycolipids and glycoproteins derived from host cell Dissolves N-acetylneuraminic acid in mucus to increase liquefaction Prevents self hemagglutination 5/13/2017 6 Classification Three antigenic types of nucleoprotein give rise to three different strains of influenza Flu A, Flu B Flu C No antigenic cross reactivity of nucleoproteins 5/13/2017 7 Gene Reassortment ANTIGENIC SHIFT Host cell is infected simultaneously with two different strains of flu Progeny viruses have mixture of gene segments because RNA multipartite Novel Type A strains gives rise to pandemics of influenza A 5/13/2017 8 Influenza 1918 Started in midwestern USA Spread to Europe on troopships Attacked healthy adults Antigenic Shift Trying to isolate cells with both strains of Virus 5/13/2017 9 Antigenic Drift Flu A Flu B undergo genetic changes in the enveloped proteins MINOR antigenic changes serologically cross reactive Causes yearly epidemics 5/13/2017 10 Influenza Subtypes Strain Influenza A first isolated Bangkok Year 79 Hemagglutinin :H1, H2, H3 Neuraminidase N1, N2 A/Bangkok/79 H3N2 Link to CDC Web site 5/13/2017 11 Flu infection cycle 5/13/2017 12 5/13/2017 13 “Original Antigenic Sin” Individual develops antibodies to flu antigens after first exposure On second exposure antigens changed inducing a new array of antibodies Antibodies to shared antigenic epitopes have higher avidity Used to identify the original infection 5/13/2017 14 Influenza Multiplication virus binds to host by hemagglutinin transcription & nucleocapside assembly in nucleus infectious virions assembled in cytoplasm bud from cell membranes cycle takes 6 hours 5/13/2017 15 Clinical Manifestations Respiratory symptoms Coryza, sore throat, cough, substernal chest pain Systemic Symptoms Headache, chills, fever (3840C), prostration 5/13/2017 16 Epidemiology Epidemic lasts 6 weeks in Jan-Feb First in school age children (5-9 years) Brought home to preschooler & adults industrial absenteeism Pneumonia influenza in elderly 5/13/2017 17 Diagnosis Clinical symptoms more likely if syndrome occurs in adults in winter a febrile respiratory epidemic is underway Detection of Virus rise in antibody titre between acute phase and convalescent phase 5/13/2017 18 Detection of Flu Virus Isolated from respiratory secretions grown in tissue culture embryonated eggs Virus identified by presence of hemagglutinin 5/13/2017 19 Tissue culture Hemadsorption Red cells adhere to virions budding from the host cell Hemagglutination inhibition Confirm with serological analysis of tissue culture fluid 5/13/2017 20 Prevention Prevention Influenza virus vaccine Treatment Amantadine 1976 effective against type A Web site Rimantadine 1993 effective against type A & type B Neuraminidase Inhibitors zanamivir and oseltamivir 5/13/2017 21 Treatment Amantadine 1976 effective against type A Web site Rimantadine 1993 effective against type A & type B Neuraminidase Inhibitors 1999 zanamivir and oseltamivir web Site 5/13/2017 22 Influenza virus vaccine Developed half a century ago virus grown in chick egg embryos inactivated with formalin One- doses administered pareenterally in the fall 50-90% effective Web site 5/13/2017 23 The national swine flu immunization of 1976 was accompanied by an increase risk of Guillain-Barre syndrome 5/13/2017 24 Guillain- Barre Syndrome AKA Acute Infectious Polyneuritis Symptoms symmetric flaccid paralysis facial paralysis Degeneration of myelin of peripheral nerves Allergic reaction 5/13/2017 25 Amantadine Amantadine hydrochloride administered for 10 days blocks viral uncoating prevents 50% of infections prevents 67% of illnesses prophylactically protects 80% 5/13/2017