Orthomyxovirus
Orthomyxovirus Outline
Structure
- multipartite genome, 7-8 segments, 10 genes
- 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
- 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
gives rise to pandemics of influenza A
Influenza 1918
- Started in midwestern USA
- Spread to Europe on troopships
- Trying to isolate cells with both strains of Virus
Antigenic Drift
- Flu A Flu B undergo genetic changes in the enveloped proteins
- serologically cross reactive
Influenza Subtypes
- Hemagglutinin :H1, H2, H3
Flu infection cycle
PPT Slide
“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
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
- more likely if
- syndrome occurs in adults in winter
- a febrile respiratory epidemic is underway
- 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
- Amantadine
- 1976 effective against type A Web site
- Rimantadine
- 1993 effective against type A & type B
- Neuraminidase Inhibitors
- zanamivir and oseltamivir 1999 web Site
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
Influenza virus vaccine
- Developed half a century ago
- virus grown in chick egg embryos
- inactivated with formalin
- One- doses administered pareenterally in the fall
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
Amantadine
- prevents 50% of infections
- prevents 67% of illnesses
- prophylactically protects 80%