醫(yī)學(xué)微生物學(xué)資料：Influenza virus

1、Influenza virus Virology and infectionEssential and minimum requirement of information for a given virusClassification of the virusStructure of the virus Life cycle of the virus replication and target cellBiological consequence and clinical profile of the virus infectionClinical and laboratory diagn

2、osis of the infectionTreatment and prevention of the infectionCategories of Respiratory VirusesOrthomyxoviridae: Influenza virusParamyxoviridae : Parainfluenza virus; Mumps virus; Measles; Respiratory syneytical virusTogaviridae: Rubella VirusCoronaviridae: Corona Virus; SARS virusAdenoviridae : hum

3、an Adenovirus picornaviridae: Rhino Virus; Reoviridae:ORTHOMYXOVIRUSESRNA plus NP protein HA - hemagglutinin polymerase complexNA - neuraminidaseInfluenza virusOrthomyxoviridae and influenza virusType A: most dangerous type with antigen changesType B: the antigen changes to a less degreeType C: stab

4、le in antigen moleculesTYPE A+yesyesyesshift, driftyesseverity of illnessanimal reservoirhuman pandemicshuman epidemicsantigenic changessegmented genomeTYPE B+nonoyesdriftyesTYPE C+nonono driftyescharacteristicInfluenza virus Type AMorphology in EM: Spherical particle about 100 nm in diameterGenome:

5、 The single-stranded,negative sense RNA as eight separate segmentsStructure: A small but complicated structure of virus. The most important components are envelopment (HA) and (NA)Influenza virus AInfluenza virus type AThe risk of this virus comes from:The segmented RNA genome, the physical facilita

6、ting of reassortment (重排）The virus circulates in humans, mammalian animals like pig and aquatic birdsHigh virulence of the virus in terms of systemic infection and inhibition of immune system of hostInhibition of immunity by virusInhibition of lymph-blood ciruculation of immuno-active cells (lymphoc

7、ytopenia)Inhibition of protein synthesis (delayed antibody response)Inhibition of antigen presentation with MHC II molecules ( poor cell-mediated immune response)Haemagglutinin (HA)Encoded by RNA segment #4 Can agglutinate red blood cells - hence the nomenclature Cleavage by host protease and result

8、s in HA1 and HA2 HA glycoprotein is the viral ligand and it stimulate neutralizing antibody responsesNeuraminadase (NA) Encoded by RNA segment #6 Enzyme that targets at neuraminic (sialic) acid on host cell surface as a substrate Important in releasing mature virus from cellsTarget molecules of OSEL

9、TAMIVIR Influenza virusAntigen Soluble antigens: include ribonucleoprotein and M protein which are much stable in antigenicity. Surface antigens: include HA and NA which are much variable in antigenicity. Antigen Change Antigen drift: a gradual change of antigen due to point mutation.Antigen shift:

10、a drastic change of antigen due to genetic reassortment. EPIDEMIC !Avian flu, a nightmare of humansInfluenza A virus comes from the avian reservoirH1,H2,H3 and H5 in humans, H1 and H3 in pigs, H3 and H7 in horsesN1 and N2 in humansH5N1, a new strain?where do “new” HA and NA come from?13 types HA 9 t

11、ypes NAall circulate in birdspigsavian and humanwhere do “new” HA and NA come from?Process of flu infectionNormal tracheal mucus membrane3 days after infection7 days after infectionClinical profile of influenzaSymptoms: chills, headache, dry cough followed by fever, generalized muscular ache, malais

12、e and anorexia. When influenza appears in an epidemic form, clinical symptoms are consistent enough to make a diagnosis without laboratory tests.Complications of influenzaPneumonia caused by virus and/or bacteriaReyes syndrome: an acute encephalopathy of patients between 2 to 16 years of ageAspirin

13、could be a risk factor!PULMONARY COMPLICATIONSSecondary infection by :Streptococcus pneumoniaeStaphlyococcus aureusHemophilus influenzae （流感嗜血桿菌）Treatment - DRUGSRIMANTADINE 金剛乙胺(M2)AMANTADINE 金剛烷胺(M2)ZANAMIVIR (NA)OSELTAMIVIR (達(dá)菲) (NA)Laboratory diagnosisIsolation of virusAnimal inoculationTissue c

14、ulture inoculationRT-PCR RNA probe technologyLaboratory diagnosisSerology hemagglutination inhibition ELISA immuno-fluoresence Clinical diagnosis of flu infectionSymptoms: fever, myalgia and catarrhEmergence of patients like an outbreak of diseaseSeasonal predisposing factorEpidemiological informati

15、onPrevention of influenzaHygiene procedures based on well identification of transmission pathwayHand hygiene is more important!PREVENTION - DRUGSRIMANTADINE 金剛乙胺(M2)AMANTADINE 金剛烷胺(M2)ZANAMIVIR (NA)OSELTAMIVIR (達(dá)菲) (NA)Active immunity Vaccine and vaccinationFlowchart of vaccine production from isola

16、tion potential virulent strain to vaccine Risks of vaccination against flu infectionCost-effectiveness of vaccinationStrategy of vaccine developmentIsolation of potentially pathogenic strainScreening of vaccine candidatesInactivation of vaccine strains and epitope identificationDevelopment and bulk

17、production of vaccine The bottle neck is chicken egg! Vaccines against fluInactivated vaccinesAttenuated vaccinesSplit vaccines Manufacturing of Monovalent Bulk VaccineSeed Suspension (WSV)Manufacturing of Final Bulk and Final LotSpecific review Staphylococcus -treatment of infectionVirus infection-different types o