Pathogenesis of Viral Infections Ability of viruses to cause disease. Viewed on two levels:

1. Pathogenesis of Viral Infections Ability of viruses to cause disease. Viewed on two levels: (1) Changes that occur within individual cells (2) Process that takes place in the infected patient.

2. THE INFECTED CELL • Four effects of viruses on the cell: • death, • (2) fusion of cells to form multinucleated cells, • (3) malignant transformation, • (4) no apparent changes

3. Death of cell means: @ inhibition of protein synthesis, @ inhibition of N.A. synthesis . Infected cells may contain inclusion bodies, eg Negri bodies, which are eosinophilic cytoplasmic inclusions found in rabies virus-infected brain.

4. @ Multinucleated giant cells form after infection with herpesviruses and paramyxoviruses. @ Diagnosis of herpesvirus skin infections is made by finding multinucleated giant cells with eosinophilic intranuclear inclusions in skin scrapings.

5. @ Viral infection of the cell is shown by the cytopathic effect (CPE). @ CPE begins with a rounding and darkening of the cell and ends in either disintegration or giant cell formation.

6. @ Detection of virus in specimen is made by appearance of CPE in cell culture. @ CPE is also used for the quantifying of viruses in samples by plaque assays

7. @ Infection with oncogenic viruses causes malignant transformation : *massive growth, *prolonged survival, *rounded, piled-up cells. @ Symbiotic relationship is rare : * cell survives & multiplies despite replication of virus.

8. THE INFECTED PATIENT Pathogenesis in infected patient involves: (I) transmission of virus & entry into host. (2) replication of virus & damage to cells. (3) spread of virus to other cells & organs. (4) immune response: host defense & a cause of diseases. (5) persistence of virus in some instances.

9. Stages of viral infection are : • an incubation period during which patient is asymptomatic. • a prodromal period during which nonspecific symptoms occur. • a specific-illness period during which symptoms and signs occur .

10. a recovery period during which the illness wanes and the patient regains good health. • In some patients, the infection persists and a chronic carrier state or a latent infection occurs .

11. Transmission & Portal of Entry • Person-to-person spread by: transfer of respiratory secretions, saliva, blood, or semen and by fecal contamination of water or food. • 2.Mother to offspring: *across the placenta, *on delivery, *during breast feeding.

12. 3. Animal-to-human transmission: * a bite of an animal (rabies) , * a bite of a mosquito,transfering virus from an animal to patient . 4. Activation of a latent virus to form an active virus, occurring within an individual, without transmission from outside .

13. Localized or Disseminated Infections @ Viral infections are either localized to portal of entry or spread through the body. @ Localized infection is common cold, involving only the URT . @ Systemic infections is paralytic poliomyelitis.

14. Persistent Viral Infections • @ Sometimes virus persists for long periods in the body either intact or as a viral component • @ Persistence of viruses is due to: • integration of a DNA provirus • into the host cell DNA: retrovirus

15. (2) immune tolerance, because neutralizing antibodies are not formed; (3) formation of virus-antibody complexes ; (4) location within an immunologically sheltered organ, e.g. the brain;

16. (5) rapid antigenic variation; (6) spread from cell to cell without an extracellular phase so that virus is not exposed to antibody; (7) immuno­suppression, as in AIDS.

17. Types of persistent infections • Chronic-Carrier Infections: • @ Carrier state can follow an • asymptomatic infection or a • symptomatic infection • @ It can either be asymptomatic or • result in chronic illness. • @ Examples are : * chronic hepatitis, • * neonatal rubella infection , • * cytomegalovirus infections.

18. B. Latent Infections: @ Best illustrated by herpesvirus @ Patient recovers from the initial infection and virus production stops. @ Later symptoms may recur, and virus is produced .

19. @ Varicella-zoster virus causes varicella (chickenpox) as its initial manifestation @ Then remains latent, primarily in the trigeminal or thoracic ganglion cells. @ It recurs in the form of painful vesicles of zoster (shingles) ,

20. C. Slow Virus Infections: @ "slow virus" refers to the long period between initial infection and onset of disease (years). @ If the virus was identified, the virus has been shown to have a normal, not a prolonged, growth cycle. @ Therefore it is not because virus growth is slow; but because I.P. & progression of disease are prolonged.

21. @ 3 of slow virus infections are : • sub­acute sclerosing panencephalitis, following measles virus infections . • progressive multifocal leukoencephalopathy (PML), following JC virus infection. • *PML occurs in patients with lymphomas or • who are immunosuppressed. • 3.Creutzfeldt-Jakob disease جنون البقر ) ) and kuru, are caused by prion atypical virus.