1 Orthomyxovirus Hugh B Fackrell FackrelUwindsor ca Filename

1 Orthomyxovirus Hugh B. Fackrell Fackrel@Uwindsor. ca Filename: orthomyx. ppt 12/3/2020

2 Orthomyxovirus Outline þStructure þClassification þMultiplication þClinical manifestations þEpidemiology þDiagnosis þControl Baron’s Web Site 12/3/2020

3 Structure þInfluenza viruses þss. RNA, antisense, þmultipartite genome, 7 -8 segments, 10 genes þspherical OR filamentous þenveloped ä hemagglutinin ä neuraminidase 12/3/2020

4 Flu Hemagglutinin þProtein in viral envelope þ 13 different hemagglutinin antigens þbinds to N-aceytlneuraminic acid on host cell glycolipids or glycoproteins þHemagglutinin hydrolysed by host cell proteases to create infectious virion 12/3/2020

5 Flu Neuraminidase þFound in the viral envelope þ 9 different neuraminidase antigens þRemoves N-acetylneuraminic acid from glycolipids and glycoproteins derived from host cell þDissolves N-acetylneuraminic acid in mucus to increase liquefaction Prevents self hemagglutination 12/3/2020

6 Classification þThree antigenic types of nucleoprotein give rise to three different strains of influenza ä Flu A, ä Flu B ä Flu C þNo antigenic cross reactivity of nucleoproteins 12/3/2020

7 Gene Reassortment ANTIGENIC SHIFT þHost cell is infected simultaneously with two different strains of flu þProgeny viruses have mixture of gene segments because RNA multipartite þNovel Type A strains gives rise to pandemics of influenza A 12/3/2020

8 Influenza 1918 þStarted in midwestern USA þSpread to Europe on troopships þAttacked healthy adults þAntigenic Shift þTrying to isolate cells with both strains of Virus 12/3/2020

9 Antigenic Drift þFlu A Flu B undergo genetic changes in the enveloped proteins þMINOR antigenic changes þserologically cross reactive Causes yearly epidemics 12/3/2020

10 Influenza Subtypes þStrain Influenza A þ first isolated Bangkok þ Year 79 þHemagglutinin : H 1, H 2, H 3 þNeuraminidase N 1, N 2 A/Bangkok/79 H 3 N 2 Link to CDC Web site 12/3/2020

11 Flu infection cycle 12/3/2020

12 12/3/2020

13 “Original Antigenic Sin” þIndividual develops antibodies to flu antigens after first exposure þOn second exposure antigens changed inducing a new array of antibodies þAntibodies to shared antigenic epitopes have higher avidity Used to identify the original infection 12/3/2020

14 Influenza Multiplication þvirus binds to host by hemagglutinin þtranscription & nucleocapside assembly in nucleus þinfectious virions assembled in cytoplasm þbud from cell membranes þcycle takes 6 hours 12/3/2020

15 Clinical Manifestations þRespiratory symptoms ä Coryza, sore throat, cough, substernal chest pain þSystemic Symptoms ä Headache, chills, fever (3840 C), prostration 12/3/2020

16 Epidemiology þEpidemic lasts 6 weeks in Jan-Feb þFirst in school age children (5 -9 years) þBrought home to preschooler & adults ä industrial absenteeism ä Pneumonia influenza in elderly 12/3/2020

17 Diagnosis þClinical symptoms þmore likely if ä syndrome occurs in adults in winter ä a febrile respiratory epidemic is underway þDetection of Virus þ rise in antibody titre between acute phase and convalescent phase 12/3/2020

18 Detection of Flu Virus þIsolated from respiratory secretions ä grown in tissue culture ä embryonated eggs þVirus identified by presence of hemagglutinin 12/3/2020

19 Tissue culture þHemadsorption ä Red cells adhere to virions budding from the host cell þHemagglutination inhibition ä Confirm with serological analysis of tissue culture fluid 12/3/2020

20 Prevention þInfluenza virus vaccine Treatment þ Amantadine ä 1976 effective against type A Web site þ Rimantadine ä 1993 effective against type A & type B þ Neuraminidase Inhibitors ä zanamivir and oseltamivir 12/3/2020

21 Treatment þAmantadine ä 1976 effective against type A Web site þ Rimantadine ä 1993 effective against type A & type B þNeuraminidase Inhibitors ä 1999 zanamivir and oseltamivir web Site 12/3/2020

22 Influenza virus vaccine þDeveloped half a century ago þvirus grown in chick egg embryos þinactivated with formalin þOne- doses administered pareenterally in the fall þ 50 -90% effective Web site 12/3/2020

23 The national swine flu immunization of 1976 was accompanied by an increase risk of Guillain-Barre syndrome 12/3/2020

24 Guillain- Barre Syndrome þAKA Acute Infectious Polyneuritis þSymptoms ä symmetric flaccid paralysis ä facial paralysis þDegeneration of myelin of peripheral nerves þAllergic reaction 12/3/2020

25 Amantadine þAmantadine hydrochloride þadministered for 10 days þblocks viral uncoating þprevents 50% of infections þprevents 67% of illnesses þprophylactically protects 80% 12/3/2020