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20 chapter viruses associated with respiratory infections

20 chapter viruses associated with respiratory infections. Department of pathogenic biology xie-shuixiang. ORTHOMYXOVIRUSES. pleomorphic influenza types A,B,C febrile, respiratory illness with systemic symptoms. ‘ FLU ’. True influenza

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20 chapter viruses associated with respiratory infections

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  1. 20 chapterviruses associated with respiratory infections Department of pathogenic biology xie-shuixiang

  2. ORTHOMYXOVIRUSES • pleomorphic • influenza types A,B,C • febrile, respiratory illness with systemic symptoms

  3. ‘FLU’ • True influenza • influenza virus A or influenza virus B (or influenza virus C infections - much milder) • Febrile respiratory disease with systemic symptoms caused by a variety of other organisms often called ‘flu’

  4. THE IMPACT OF INFLUENZAPANDEMICS Deaths:

  5. INFLUENZA VIRUS

  6. Composition of Influenza Virus 1.Core RNA： -ssRNA, 8 fragments NP (nucleoprotein) RNA dependent RNA polymerase 2. envelope M protein lipid envelope sipke hemagglutinin(HA) 5 neuraminidase(NA) 1

  7. HA - hemagglutinin NA - neuraminidase helical nucleocapsid (RNA plus NP protein) lipid bilayer membrane polymerase complex M1 protein type A, B, C : NP, M1 protein sub-types: HA or NA protein

  8. Nomenclature Host of origin geographical origin strain number parentheses antigenic description of HA and NA e.g. A/swine/Iowa/3/70(H1N1) A/Hong Kong/1/68(H3N2)

  9. Functions of Hemagglutinin • HA causes agglutination of red blood cells. • Viruses bind to the mucous membrane cells by HA1 interacting with membrane receptor. • Virus’ envelope fuse with cell membrane by HA2 forming a fusion pore.

  10. S S cell enzymes S S acid pH S S HA protein - attachment, fusion

  11. Functions of Neuraminidase • NA help the virus to permeate mucin and escape from “non-specific”inhibitor. • NA can increase the number of free virus particles, hence more virus spread from the original site of infection. • NA is important in the final stages of release of the new virus particle from infected cells.

  12. NA protein - neuraminidase

  13. ANTIGENIC DRIFT • Minor changes in antigens due to gene mutation in influenza virus. • HA and NA accumulate mutations • RNA virus • immune response no longer protects fully • sporadic outbreaks, limited epidemics

  14. ANTIGENIC SHIFT • Major changes in antigens due to gene reassortment in influenza virus. • “new” HA or NA proteins • pre-existing antibodies do not protect • may get pandemics

  15. INFLUENZA A PANDEMICS Ryan et al., in Sherris Medical Microbiology

  16. where do “new” HA and NA come from? • 15 types HA • 9 types NA • all circulate in birds • pigs • avian and human

  17. where do “new” HA and NA come from?

  18. why do we not have influenza B pandemics? • so far no shifts have been recorded • no animal reservoir known

  19. TRANSMISSION • AEROSOL • 100,000 TO 1,000,000 VIRIONS PER DROPLET • 18-72 HR INCUBATION • SHEDDING

  20. DECREASED CLEARANCE • RISK BACTERIAL INFECTION • VIREMIA RARE Lycke and Norrby Textbook of Medical Virology 1983

  21. RECOVERY • INTERFERON - SIDE EFFECTS INCLUDE: • FEVER, MYALGIA, FATIGUE, MALAISE • CELL-MEDIATED IMMUNE RESPONSE • TISSUE REPAIR • CAN TAKE SOME TIME

  22. INTERFERON

  23. antiviral state antiviral state antiviral state antiviral state INTERFERON

  24. antiviral state antiviral state antiviral state antiviral state INTERFERON

  25. antiviral state antiviral state antiviral state antiviral state INTERFERON

  26. PROTECTION AGAINST RE-INFECTION • IgG and IgA • IgG less efficient but lasts longer • antibodies to both HA and NA important • antibody to HA more important (can neutralize)

  27. SYMPTOMS • FEVER • HEADACHE • MYALGIA • COUGH • RHINITIS • OCULAR SYMPTOMS

  28. CLINICAL FINDINGS • SEVERITY • VERY YOUNG • ELDERLY • IMMUNO-COMPROMISED • HEART OR LUNG DISEASE

  29. PULMONARY COMPLICATIONS • CROUP (YOUNG CHILDREN) • PRIMARY INFLUENZA VIRUS PNEUMONIA • SECONDARY BACTERIAL INFECTION • Streptococcus pneumoniae • Staphlyococcus aureus • Hemophilus influenzae

  30. DIAGNOSIS • ISOLATION • NOSE, THROAT SWAB • TISSUE CULTURE OR EGGS • SEROLOGY • RAPID TESTS • provisional - clinical picture + outbreak

  31. VACCINE • ‘BEST GUESS’ OF MAIN ANTIGENIC TYPES • CURRENTLY • type A - H1N1 • type A - H3N2 • type B • each year choose which variant of each subtype is the best to use for optimal protection

  32. VACCINE • inactivated • egg grown • sub-unit vaccine for children • reassortant live vaccine approved 2003 • for healthy persons (those not at risk for complications from influenza infection) ages 5-49 years

  33. live vaccine development adapted from Treanor JJ Infect. Med. 15:714

  34. TREATMENT - DRUGS • RIMANTADINE (M2) • type A only, needs to be given early • AMANTADINE(M2) • type A only, needs to be given early • ZANAMIVIR (NA) • types A and B, needs to be given early • OSELTAMIVIR (NA) • types A and B, needs to be given early

  35. NA protein - neuraminidase . . . . . . . . . . . . . . . . . . .

  36. OTHER TREATMENT • REST, LIQUIDS, ANTI-FEBRILE AGENTS (NO ASPIRIN FOR AGES 6MTHS-18YRS) • BE AWARE OF COMPLICATIONS AND TREAT APPROPRIATELY

  37. CORONAVIRUSES COLDS AND  SARS

  38. Severe acute respiratory syndrome (SARS)

  39. SARS Coronavirus, SARS CoV • Severe Acute Respiratory Syndrome(SARS) • 2002/11

  40. SARS symtom • Droplet or osculation • Latent period：2~12d，usually4~5d • Centralization in family and hospital apparently

  41. Biological properties • 60-130nm，envelope with spikes • +ssRNA，29.7KB，14 ORF:RNApolymer- ase、S、E、M、N • Vero cell--CPE • Infected quadrumana –typical SARS symptom

  42. SARS Genome

  43. Transmission and Epidemiology

  44. Chinese SARS epidemiology

  45. Diagnosis • Mainly depend on the clinic and epidemiologic data • Pathogen diagnosis • Isolation and identification of virus • RT-PCR • Immunofluorescence、ELISA • P3 laboratory • Pathogen diagnosis is immature

  46. Prevention • SARS CoV比普通CoV抵抗力强，室温下痰、粪便、尿中可稳定存活1~2d • 对温度敏感，37oC存活4d，56oC存活90m，75oC30m • 对含氯消毒剂、过氧乙酸及UV均敏感， • WHO推荐中效以上的消毒剂，如过氧乙酸

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