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RETROVIRUSES AND AIDS

RETROVIRUSES AND AIDS. HIV-1 & HIV-2 1978: Robert Gallo: HTLV-1/ lymphocytes of leukemia patients HTLV-2 1981: AIDS: . Homosexual male: . Pneumocystic carinii . Kaposi`s sarcoma . 1983: Montagnier & Barre-Sinoussi/Pasteur Institute

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RETROVIRUSES AND AIDS

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  1. RETROVIRUSES AND AIDS

  2. HIV-1 & HIV-2 1978: Robert Gallo: HTLV-1/ lymphocytes of leukemia patients HTLV-2 1981: AIDS: . Homosexual male: . Pneumocysticcarinii . Kaposi`s sarcoma . 1983: Montagnier & Barre-Sinoussi/Pasteur Institute . Isolate HIV-1 (Confirmed by Robert Gallo/USA) . HIV-2 / Africa

  3. HIV and AIDS Two rare diseases in the gay community linked to IMMUNOSUPPRESSION OPPORTUNISTIC INFECTIONS Also Lymphadenopathy • Gay-Related Immune Deficiency • Acquired Immune Deficiency Syndrome (AIDS)

  4. HIV and AIDS Distinguishing characteristics • Clusters of infected men • Apparent concentration within sexually interactive groups • High numbers of sex partners Suggests an infectious agent

  5. HIV and AIDS More evidence for an infectious agent Different ways of getting a similar syndrome • Blood transfusions • Intravenous drug use • Hemophilia (clotting factor) Female sex partners of AIDS-positive IV drug users and hemophiliacs Not just in the Gay community

  6. HIV and AIDS Obvious agent: A virus……that is now in the blood supply Primary route of transmission: Sex AIDS is a sexually-transmitted viral disease

  7. PROPERTIES Classification • Retroviridae • Reverse transcriptase (RT) Morphology • Icosahedral, 100 nm • Enveloped

  8. Genome • +ssRNA (2 copies) • Several copies of RT, integrase, proteases • env gene :gp120 + gp41(gp160) • gag = : p24 • pol = : RT, integrase, protease

  9. Replication of retrovirus

  10. CLINICAL ASPECTS • IP: 3-4 W • Stage A: Influenza-like illness: 60% of infected individual move to • Stage B: AIDS-related complex: =4 years, fever, weight loss, persistent lymphadenopathy, night sweats, and diarrhea • Stage C: Full-blown AIDS: Thrush, herpes zoster, Pneumocystis carinii pneumonia • Time: Start Death : 10 years (70%), rest: 17 years; Long- term survivors or non- progressor`s group.

  11. The clinical manifestation: • Malignant disease: . Kaposi`s sarcoma, common . B-cell lymphoma . Non-Hodgkins lymphoma . Genital cancers • Infective manifestations: . Many opportunistic infections

  12. Neurological sequelae • Involve CNS:Loss of memory & balance Aids in children: • Infected by: - Transplantation - During delivery, blood contact - Breast milk * Azidothymidine (AZT) to pregnant women: Reduce the transmission

  13. PATHOGENESIS Transmission

  14. IMMUNE RESPONSE p24 Ags appear at early stage of infection followed by Ab to gp120 + gp41 then Abs to p24

  15. The time course of development of HIV antigens and antibodies

  16. EPIDEMIOLOGY * 1 (Infected reported case) 10 (Infected not reported)  100 (Carrier) * Two distinct genetic variation: - M (Major): 8 genetic subtypes (A-H) . B subtypes: Europe & USA (Homosexual) . C & E: Africa (Heterosexual) - Out-lier (O)

  17. AIDS Statistics • Approximately 44,000,000 people in the world are HIV- • infected • Approximately 14,000 new HIV infections occur daily around • the world • Over 90% of these are in developing countries • 1000 are in children less than 15 years of age. • Of adult infections, 48% are in women and 15% in • individuals 15-25 years • As of December 2003, 929,985 Americans reported with • AIDS. • At least 501,669 of them have died (2002 figures) • 5,315 children under 15

  18. LABORATORY DIAGNOSIS • ELISA: Abs to env protein • Confirmed by western blot analysis • Viral genome load assay: Increase RNA copies  Increase onset of AIDS • New test: Saliva • VPR37 protein • 20 min. • Accuracy 99%

  19. HIV VACCINE • Inactivated whole-virus vaccine: Weak immune response • Recombinant DNA techniques (env gene: gp160 or gp120): Yeast & E.coli: No satisfactory protection • Live attenuated HIV vaccine (Mutate or alter nef gene: Increase viral replication & spread): Under investigation

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