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OrthomyxovirusOrthomyxovirus
Hugh B. FackrellHugh B. Fackrell
[email protected]@Uwindsor.ca
Filename: orthomyx.pptFilename: orthomyx.ppt
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Orthomyxovirus OutlineOrthomyxovirus Outline
StructureStructureClassificationClassificationMultiplicationMultiplicationClinical manifestationsClinical manifestationsEpidemiologyEpidemiologyDiagnosisDiagnosisControlControl
Baron’s Web SiteBaron’s Web Site
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StructureStructure
Influenza virusesInfluenza virusesssRNA, antisense, ssRNA, antisense, multipartite genome, 7-8 multipartite genome, 7-8
segments, 10 genessegments, 10 genesspherical spherical OROR filamentous filamentousenvelopedenveloped
hemagglutinin hemagglutinin neuraminidaseneuraminidase
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Flu Hemagglutinin Flu Hemagglutinin
Protein in viral envelopeProtein in viral envelope13 different hemagglutinin antigens13 different hemagglutinin antigensbinds to N-aceytlneuraminic acid on host binds to N-aceytlneuraminic acid on host
cell glycolipids or glycoproteinscell glycolipids or glycoproteinsHemagglutinin hydrolysed by host cell Hemagglutinin hydrolysed by host cell
proteases to create infectious virionproteases to create infectious virion
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Flu NeuraminidaseFlu Neuraminidase
Found in the viral envelopeFound in the viral envelope9 different neuraminidase antigens9 different neuraminidase antigensRemoves N-acetylneuraminic acid from Removes N-acetylneuraminic acid from
glycolipids and glycoproteins derived from glycolipids and glycoproteins derived from host cellhost cell
Dissolves N-acetylneuraminic acid in Dissolves N-acetylneuraminic acid in mucus to increase liquefactionmucus to increase liquefaction
Prevents self hemagglutinationPrevents self hemagglutination
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ClassificationClassification
Three antigenic types of nucleoprotein give rise Three antigenic types of nucleoprotein give rise to three different strains of influenzato three different strains of influenza Flu A,Flu A, Flu BFlu B Flu CFlu C
No antigenic cross reactivity of nucleoproteinsNo antigenic cross reactivity of nucleoproteins
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Gene ReassortmentANTIGENIC SHIFT ANTIGENIC SHIFT
Gene ReassortmentANTIGENIC SHIFT ANTIGENIC SHIFT
Host cell is infected simultaneously with Host cell is infected simultaneously with two different strains of flutwo different strains of flu
Progeny viruses have mixture of gene Progeny viruses have mixture of gene segments because RNA multipartitesegments because RNA multipartite
Novel Type A strainsNovel Type A strains
gives rise to gives rise to pandemicspandemics of of influenza Ainfluenza A
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Influenza 1918Influenza 1918
Started in midwestern USAStarted in midwestern USASpread to Europe on troopshipsSpread to Europe on troopshipsAttacked healthy adultsAttacked healthy adultsAntigenic ShiftAntigenic ShiftTrying to isolate cells with both strains of Trying to isolate cells with both strains of
VirusVirus
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Antigenic DriftAntigenic Drift
Flu A Flu B undergo genetic changes in the Flu A Flu B undergo genetic changes in the enveloped proteinsenveloped proteins
MINOR antigenic changesMINOR antigenic changesserologically cross reactive serologically cross reactive
Causes yearly Causes yearly epidemicsepidemics
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Influenza SubtypesInfluenza Subtypes
Strain Influenza Strain Influenza AA first isolated first isolated BangkokBangkok Year Year 7979Hemagglutinin :H1, H2, Hemagglutinin :H1, H2, H3H3Neuraminidase N1, Neuraminidase N1, N2N2
A/Bangkok/79 H3N2A/Bangkok/79 H3N2
Link to CDC Web site
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“Original Antigenic Sin”“Original Antigenic Sin”
Individual develops antibodies to flu Individual develops antibodies to flu antigens after first exposureantigens after first exposure
On second exposure antigens changed On second exposure antigens changed inducing a new array of antibodiesinducing a new array of antibodies
Antibodies to shared antigenic epitopes Antibodies to shared antigenic epitopes have higher avidityhave higher avidity
Used to identify the original infectionUsed to identify the original infection
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Influenza MultiplicationInfluenza Multiplication
virus binds to host by hemagglutininvirus binds to host by hemagglutinintranscription & nucleocapside assembly in transcription & nucleocapside assembly in
nucleusnucleusinfectious virions assembled in cytoplasminfectious virions assembled in cytoplasmbud from cell membranesbud from cell membranescycle takes 6 hourscycle takes 6 hours
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Clinical ManifestationsClinical Manifestations
Respiratory symptomsRespiratory symptomsCoryza, sore throat, cough, Coryza, sore throat, cough,
substernal chest painsubsternal chest painSystemic SymptomsSystemic Symptoms
Headache, chills, fever (38-Headache, chills, fever (38-40C), prostration40C), prostration
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EpidemiologyEpidemiology
Epidemic lasts 6 weeks in Jan-FebEpidemic lasts 6 weeks in Jan-FebFirst in school age children (5-9 years)First in school age children (5-9 years)Brought home to preschooler & adultsBrought home to preschooler & adults
industrial absenteeismindustrial absenteeism Pneumonia influenza in elderlyPneumonia influenza in elderly
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DiagnosisDiagnosis
Clinical symptomsClinical symptomsmore likely if more likely if
syndrome occurs in adults in wintersyndrome occurs in adults in wintera febrile respiratory epidemic is underwaya febrile respiratory epidemic is underway
Detection of VirusDetection of Virus rise in antibody titre between acute phase and rise in antibody titre between acute phase and
convalescent phaseconvalescent phase
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Detection of Flu VirusDetection of Flu Virus
Isolated from respiratory secretionsIsolated from respiratory secretions grown in tissue culturegrown in tissue cultureembryonated eggsembryonated eggs
Virus identified by presence of Virus identified by presence of hemagglutininhemagglutinin
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Tissue cultureTissue culture
HemadsorptionHemadsorptionRed cells adhere to virions budding from Red cells adhere to virions budding from
the host cellthe host cellHemagglutination inhibitionHemagglutination inhibition
Confirm with serological analysis of tissue Confirm with serological analysis of tissue culture fluidculture fluid
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PreventionPrevention
Prevention Prevention Influenza virus Influenza virus
vaccinevaccine
Treatment Treatment AmantadineAmantadine
1976 effective against 1976 effective against type A type A Web siteWeb site
RimantadineRimantadine 1993 effective against type A 1993 effective against type A
& type B& type B
Neuraminidase InhibitorsNeuraminidase Inhibitors zanamivir and oseltamivir zanamivir and oseltamivir
1999 1999 web Siteweb Site
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TreatmentTreatment
AmantadineAmantadine 1976 effective against type A 1976 effective against type A Web siteWeb site
RimantadineRimantadine 1993 effective against type A & type B1993 effective against type A & type B
Neuraminidase InhibitorsNeuraminidase Inhibitors 1999 zanamivir and oseltamivir1999 zanamivir and oseltamivir web Siteweb Site
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Influenza virus vaccineInfluenza virus vaccine
Developed half a century agoDeveloped half a century agovirus grown in chick egg embryosvirus grown in chick egg embryosinactivated with formalininactivated with formalinOne- doses administered pareenterally in One- doses administered pareenterally in
the fallthe fall50-90% effective50-90% effective
Web site
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The national swine flu immunization of 1976 was
accompanied by an increase risk of Guillain-Barre syndrome
The national swine flu immunization of 1976 was
accompanied by an increase risk of Guillain-Barre syndrome
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Guillain- Barre SyndromeGuillain- Barre Syndrome
AKA Acute Infectious PolyneuritisAKA Acute Infectious PolyneuritisSymptomsSymptoms
symmetric flaccid paralysissymmetric flaccid paralysis facial paralysisfacial paralysis
Degeneration of myelin of peripheral Degeneration of myelin of peripheral nervesnerves
Allergic reactionAllergic reaction
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AmantadineAmantadine
Amantadine hydrochlorideAmantadine hydrochlorideadministered for 10 daysadministered for 10 daysblocks viral uncoatingblocks viral uncoatingprevents 50% of infectionsprevents 50% of infectionsprevents 67% of illnessesprevents 67% of illnessesprophylactically protects 80%prophylactically protects 80%