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Hugh B. Fackrell Fackrel@Uwindsor.ca Filename: orthomyx.ppt
Orthomyxovirus Hugh B. Fackrell Filename: orthomyx.ppt
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Orthomyxovirus Outline
Structure Classification Multiplication Clinical manifestations Epidemiology Diagnosis Control Baron’s Web Site
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Structure Influenza viruses ssRNA, antisense,
multipartite genome, 7-8 segments, 10 genes spherical OR filamentous enveloped hemagglutinin neuraminidase
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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
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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
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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
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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
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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
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Antigenic Drift Flu A Flu B undergo genetic changes in the enveloped proteins MINOR antigenic changes serologically cross reactive Causes yearly epidemics
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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
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Flu infection cycle
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“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
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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
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Clinical Manifestations
Respiratory symptoms Coryza, sore throat, cough, substernal chest pain Systemic Symptoms Headache, chills, fever (38-40C), prostration
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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
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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
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Detection of Flu Virus Isolated from respiratory secretions
grown in tissue culture embryonated eggs Virus identified by presence of hemagglutinin
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Tissue culture Hemadsorption
Red cells adhere to virions budding from the host cell Hemagglutination inhibition Confirm with serological analysis of tissue culture fluid
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Prevention Prevention Influenza virus vaccine Rimantadine Treatment
Amantadine 1976 effective against type A Web site Rimantadine 1993 effective against type A & type B Neuraminidase Inhibitors zanamivir and oseltamivir 1999 web Site Prevention Influenza virus vaccine
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Treatment Amantadine Rimantadine Neuraminidase Inhibitors
1976 effective against type A Web site Rimantadine 1993 effective against type A & type B Neuraminidase Inhibitors 1999 zanamivir and oseltamivir web Site
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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
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The national swine flu immunization of 1976 was accompanied by an increase risk of Guillain-Barre syndrome
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Guillain- Barre Syndrome
AKA Acute Infectious Polyneuritis Symptoms symmetric flaccid paralysis facial paralysis Degeneration of myelin of peripheral nerves Allergic reaction
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Amantadine Amantadine hydrochloride administered for 10 days
blocks viral uncoating prevents 50% of infections prevents 67% of illnesses prophylactically protects 80%
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