Hugh B. Fackrell Fackrel@Uwindsor.ca Filename: orthomyx.ppt Orthomyxovirus Hugh B. Fackrell Fackrel@Uwindsor.ca Filename: orthomyx.ppt

Orthomyxovirus Outline Structure Classification Multiplication Clinical manifestations Epidemiology Diagnosis Control Baron’s Web Site

Structure Influenza viruses ssRNA, antisense, multipartite genome, 7-8 segments, 10 genes spherical OR filamentous enveloped hemagglutinin neuraminidase

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

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

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

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

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

Antigenic Drift Flu A Flu B undergo genetic changes in the enveloped proteins MINOR antigenic changes serologically cross reactive Causes yearly epidemics

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

Flu infection cycle

“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

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

Clinical Manifestations Respiratory symptoms Coryza, sore throat, cough, substernal chest pain Systemic Symptoms Headache, chills, fever (38-40C), prostration

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

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

Detection of Flu Virus Isolated from respiratory secretions grown in tissue culture embryonated eggs Virus identified by presence of hemagglutinin

Tissue culture Hemadsorption Red cells adhere to virions budding from the host cell Hemagglutination inhibition Confirm with serological analysis of tissue culture fluid

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

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

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

The national swine flu immunization of 1976 was accompanied by an increase risk of Guillain-Barre syndrome

Guillain- Barre Syndrome AKA Acute Infectious Polyneuritis Symptoms symmetric flaccid paralysis facial paralysis Degeneration of myelin of peripheral nerves Allergic reaction

Amantadine Amantadine hydrochloride administered for 10 days blocks viral uncoating prevents 50% of infections prevents 67% of illnesses prophylactically protects 80%