1. Pathogenesis CHapter32 Prepared by : Riham Alakhras

2. Introduction The ability of viruses to cause disease can be viewed on two distinct levels: (1) the changes that occur within individual cells and (2) the process that takes place in the infected patient.

3. The Infected Cell There are four main effects of virus infection on the cell: (1) death, (2) fusion of cells to form multinucleated cells, (3) malignant transformation, and (4) no apparent morphologic or functional change.

4. Death of the cell is probably due to inhibition of macromolecular synthesis. Inhibition of host cell protein synthesis frequently occurs first and is probably the most important effect.

5. Inhibition of DNA and RNA synthesis may be a secondary effect. It is important to note that synthesis of cellular proteins is inhibited but viral protein synthesis still occurs.

6. For example, poliovirus inactivates an initiation factor (IF) required for cellular mRNA to be translated into cellular proteins, but poliovirus mRNA has a special ribosome- initiating site that allows it to bypass the IF so that viral proteins can be synthesized.

7. Infected cells frequently contain inclusion bodies, which are discrete areas containing viral proteins or viral particles. They have a characteristic intranuclear or intracytoplasmic location and appearance depending on the virus.

8. One of the best examples of inclusion bodies that can assist in clinical diagnosis is that of Negri bodies, which are eosinophilic cytoplasmic inclusions found in rabies virus–infected brain neurons.

9. Another important example is the owl's eye inclusion seen in the nucleus of cytomegalovirus- infected cells. Electron micrographs of inclusion bodies can also aid in the diagnosis when virus particles of typical morphology are visualized.

10. Fusion of virus-infected cells produces multinucleated giant cells, which characteristically form after infection with herpesviruses and paramyxoviruses. Fusion occurs as a result of cell membrane changes, which are probably caused by the insertion of viral proteins into the membrane.

11. The clinical diagnosis of herpesvirus skin infections is aided by the finding of 1-multinucleated giant cells 2-eosinophilic intranuclear inclusions in skin scrapings.

12. A hallmark of viral infection of the cell is the cytopathic effect (CPE). This change in the appearance of the infected cell usually begins with a rounding and darkening of the cell and culminates in either lysis (disintegration) or giant cell formation. is an important method for quantifying the amount of virus in a sample.

13. Infection with certain viruses causes malignant transformation, which is characterized by unrestrained growth, prolonged survival, and morphologic changes such as focal areas of rounded, piled-up cells

14. Infection of the cell accompanied by virus production can occur without morphologic or gross functional changes.

15. The Infected Patient Pathogenesis in the infected patient involves (1) transmission of the virus and its entry into the host; (2) replication of the virus and damage to cells; (3) spread of the virus to other cells and organs;

16. (4) the immune response, both as a host defense and as a contributing cause of certain diseases; and (5) persistence of the virus in some instances.

17. The stages of a typical viral infection are the same as those described for a bacterial infection These stages are ?????

18. incubation period prodromal period specific-illness period recovery period

19. Transmission & Portal of Entry Viruses are transmitted to the individual by many different routes, and their portals of entry are varied

20. Main Portal of Entry of Important Viral Pathogens.

21. Portal of EntryVirusDisease Respiratory tract1Influenza virusInfluenza RhinovirusCommon cold Respiratory syncytial virusBronchiolitis Epstein-Barr virusInfectious mononucleosis Varicella-zoster virusChickenpox Herpes simplex virus type 1Herpes labialis CytomegalovirusMononucleosis syndrome Measles virusMeasles Mumps virusMumps Rubella virusRubella HantavirusPneumonia AdenovirusPneumonia

22. influenza virus

23. Rhinovirus

24. Respiratory Syncytial Virus.

25. Epstein-Barr virus

26. Varicella zoster virus

28. herpes simplex virus 1

29. Cytomegalovirus

30. Measles

31. mumps virus

32. Rubella virus

33. Hantavirus

34. adenovirus

35. Gastrointestinal tract Hepatitis A virusHepatitis A PoliovirusPoliomyelitis RotavirusDiarrhea SkinRabies virusRabies Yellow fever virus Yellow fever Dengue virusDengue Human papillomavirus Papillomas (warts)

36. Hepatitis A virus

37. poliovirus

38. Rotavirus

39. Rabies virus

40. yellow fever virus

41. Dengue virus

42. Human papillomavirus

43. Genital tractHuman papillomavirus Papillomas (warts) Hepatitis B virusHepatitis B Human immunodeficienc y virus AIDS Herpes simplex virus type 2 Herpes genitalis and neonatal herpes

44. hepatitis B

45. Human Immunodeficiency Virus

46. herpes simplex virus type 2

47. BloodHepatitis B virusHepatitis B Hepatitis C virusHepatitis C Hepatitis D virusHepatitis D Human T-cell lymphotropic virus Leukemia Human immunodeficiency virus AIDS CytomegalovirusMononucleosis syndrome or pneumonia TransplacentalCytomegalovirusCongenital abnormalities RubellaCongenital abnormalities

48. Hepatitis C

49. HEPATITIS D

50. associated cutaneous lymphoma Human T-cell lymphotropic virus

51. Viruses that Commonly Cause Perinatal Infections

52. Type of TransmissionVirus TransplacentalCytomegalovirus Parvovirus B19 Rubella virus

53. Parvovirus B19 virus

54. Hepatitis B virusAt time of birth Hepatitis C virus Herpes simplex virus type-2 Human immunodeficiency virus Human papillomavirus CytomegalovirusBreast feeding Human T-cell lymphotropic virus

55. Animal-to-human transmission can take place either directly from the bite of a reservoir host as in rabies or indirectly through the bite of an insect vector, such as a mosquito, which transfers the virus from an animal reservoir to the person.

56. Medically Important Viruses that Have an Animal Reservoir.

58. Localized or Disseminated Infections Viral infections are either localized to the portal of entry or spread systemically through the body. The best example of the localized infection is the common cold, which involves only the upper respiratory tract

59. Influenza is localized primarily to the upper and lower respiratory tracts. One of the best-understood systemic viral infections is paralytic poliomyelitis

60. After poliovirus is ingested, it infects and multiplies within the cells of the small intestine and then spreads to the mesenteric lymph nodes, where it multiplies again. It then enters the bloodstream and is transmitted to certain internal organs, where it multiplies again.

61. The virus reenters the bloodstream and is transmitted to the central nervous system, where damage to the anterior horn cells occurs, resulting in the characteristic muscle paralysis.

63. Primary viremia refers to the initial spread of virus in the blood from the first site of infection. Secondary viremia occurs when primary viremia has resulted in infection of additional tissues via bloodstream, in which the virus has replicated and once more entered the circulation.

64. poliomyelitis

65. Viral replication in the gastrointestinal tract results in the presence of poliovirus in the feces, thus perpetuating its transmission to others.

66. Some of the molecular determinants of pathogenesis have been determined by using reovirus infection in mice as a model system. This virus has three different outer capsid proteins, each of which has a distinct function in determining the course of the infection.

67. One of the proteins binds to specific receptors on the cell surface and thereby determines tissue tropism. A second protein conveys resistance to proteolytic enzymes in the gastrointestinal tract and acts as the antigen that stimulates the cellular immune response.

68. The third protein inhibits cellular RNA and protein synthesis, leading to death of the cell. Alternatively, this third protein can play a role in the initiation of persistent viral infection.

69. MAY ALLAH LEAD YOU ALL TO SUCCESS !!!