This document summarizes Orthomyxoviruses and Paramyxoviruses. It describes a case of a man who experienced influenza-like symptoms and notes that influenza viruses have segmented negative-sense RNA genomes and cause annual epidemics through antigenic drift. It then discusses the structure and replication of influenza viruses, noting their envelope proteins HA and NA. The document also summarizes pathogenesis, immunity, diagnosis, treatment and prevention of influenza. It then briefly introduces paramyxoviruses and describes two clinical cases, one involving measles characterized by Koplik's spots and rash, and one involving croup caused by parainfluenza virus.

1. OrthomyxovirusParamyxovirusesEDWARD-BENGIE L. MAGSOMBOL, MDFPCP, FPCC, DASNCAssociate Professor, Department of MicrobiologyFatima College of Medicine

2. A 22-year old man suddenly experienced headache, myalgia, malaise, dry cough, and fever. He basically felt “lousy”. After a couple of days, he had a sore throat, his cough had worsened, and he started to feel nauseated and vomited. Several of his family members had experienced similar symptoms during the previous two weeks.

3. Characteristics:Influenza A, B and C the only members

4. Enveloped virion; inactivated by detergents

5. Segmented negative-sense RNA genome with eight nucleocapsid segments

6. Genetic instability responsible for annual epidemics (mutation:drift) and periodic pandemics (reassortment: shift)Structure & Replication:Envelope with two group-specific glycoproteins:Hemagglutinin (HA)Functions:Viral attachment protein – bind to sialic acid on epithelial cell surface receptorsPromotes fusion of the envelope to the cell membraneHemagglutinates human, chicken and guinea pig rbcElicits protective neutralizing antibody response

7. Structure & Replication:Envelope with two group-specific glycoproteins:Neuraminidase (NA)With enzyme activity

8. Cleaves the sialic acid on glycoproteins, including the cell receptor  prevents clumping & facilitates release of virus from infected cells

9. Target for two antiviral drugs: zanamivir (Relenza) and oseltamivir (Tamiflu)Structure & Replication:Type-specific proteins: used to differentiate among influenza A, B, and C virusesMatrix protein (M1)Viral structural protein

10. Interacts with nucleocapsid & envelope  promotes assemblyMembrane protein (M2)Forms membrane channel

11. Facilitates uncoating & HA production

12. Target for amantadineNucleocapsid proteins (NP)

13. Structure & Replication:Transcribes and replicates its genome in the target cell nucleus

14. Assembles and buds from the plasma membranePathogenesis & Immunity:Virus first targets & kills mucus-secreting, ciliated, and other epithelial cells  loss of primary defense system

15. Cleavage of sialic acid residues of mucus by NA  provide access to tissues

16. Preferential release of the virus at the apical surface of epithelial cells and into the lungs  promote cell-to-cell spread & transmission to other hostsPathogenesis & Immunity:Spread to lower respiratory tract  shedding of bronchial or alveolar epithelium

17. Promotes bacterial adhesion to the epithelial cells  pneumonia

18. Histologic: inflammatory response of mucosal membrane (primarily monocytes & lymphocytes) with submucosaledemaPathogenesis & Immunity:Systemic symptoms due to the interferon and lymphokine response to the virus

19. Local symptoms due to epithelial cell damage

20. Interferon & CMI responses (NK & T cell) important for immune resolution and immunopathogenesis classic symptoms associated with interferon induction

21. Antibody important for future protection against infection Major contributors to pathogenesisAntibody Future protectionImmune responseT-cell responseLess frequent outcomesInterferon inductionDesquamation of mucus-secreting and ciliated cellsAerosol inoculation of virusReplication in resp. tractInfluenza syndromePneumonia Secondary bacterial pneumoniaPrimary viral pneumoniaCNS/muscle involvement

22. Why is influenza difficult to control even when there is vaccination available?

23. Antigenic Changes:Antigenic driftMinor change

24. Mutation of the HA and NA genes

25. Occurs every 2 to 3 years

26. Cause local outbreaks of influenza A & BAntigenic shiftMajor change

27. Result from re-assortment of genomes among different strains, including animal strains

28. Associated with pandemics

29. Occurs only with influenza AChicken influenza virusHuman influenza virusLung cellRe-assortment of RNA genome segmentsNew strain of influenza virus

30. How is the virus transmitted?

31. Virus is spread by inhalation of aerosol droplets expelled during talking, breathing, and coughing.

32. Virus likes cool, less humid atmosphere

33. Virus is extensively spread by school children. Who is at risk?

34. Seronegative people.Adults: classic “flu” syndromeChildren: asymptomatic to severe respiratory tract infectionHigh-risk Groups:Elderly

35. Immunocompromised people

36. People with underlying cardiac or respiratory problems (including people with asthma and smokers)What are the clinical syndromes associated with the virus? What are the possible complications?

37. Diseases Associated with Influenza Virus Infections

38. How would the diagnosis of influenza be confirmed?

39. Laboratory Diagnosis of Influenza Virus Infection

40. Which antiviral drugs are effective for the treatment of influenza virus infection? What are the targets & mechanisms of action of these drugs?

41. Amantadine, RimantadineTarget: M2 protein  inhibit an uncoating step

42. Do not affect influenza B or C virusZanamivir (Relenza) & Oseltamivir (Tamiflu)Target: neuraminidase  prevent release of virus from infected cells

43. Inhibit both influenza A and B

44. Effective for prophylaxis and for treatment during the first 24 to 48 hours after the onset of influenza A illnessWhat is the best way to control the virus?

45. The best way to control the virus is through IMMUNIZATION!Killed vaccine representing the “strains of the year”

46. Killed (formalin-inactivated) whole-virus vaccine

47. Detergent-treated virion preparations and HA- and NA-containing detergent extracts of virus

48. Vaccination routinely recommended for the elderly and people with chronic pulmonary or heart disease.PARAMYXOVIRUSES

49. Properties of Orthomyxoviruses and Paramyxoviruses

50. Members of the Family Paramyxoviridae

51. Members of the Family Paramyxoviridae

52. Unique Features of the ParamyxoviridaeLarge virion with helical nucleocapsid

53. Negative RNA genome

54. Envelope containing viral attachment protein (HN, paramyxovirus and mumps virus; H, measles virus, and G, RSV) and a fusion protein (F)

55. HN with hemagglutinin & neuraminidase activity

56. H with hemagglutinin activity

57. G without hemagglutinin or neuraminidase acvitity

58. Replicates in cytoplasm

59. Penetrate the cell by fusion with and exit by budding from the plasma membrane

60. Induce cell-to-cell fusion  multinucleated giant cellsEnvelope Spikes of Paramyxoviruses1The measles and mumps fusion proteins are also hemolysins.2In mumps and parainfluenza viruses, the hemagglutinin and neuraminidase are on the same spike and the fusion protein is on a different spike.

61. An 18-year old college freshman complained of a cough, runny nose, and conjunctivitis. The physician in the campus health center noticed small white lesions inside the patient’s mouth. The next day, a confluent red rash covered his face and neck.

62. How is the disease transmitted?

63. What clinical characteristics of this case were diagnostic for measles?