110/1/2015 Orthomyxovirus Hugh B. Fackrell [email protected] Filename: orthomyx.ppt.

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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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Flu infection

cycle

Flu infection

cycle

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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%