1. Retrovirus

2. Retroviridae include 3 subfamilies:
Oncovirinae: HTLV-1, HTLV-2
 Spumavirinae:
Lentivirinae: HIV

3. Common properties:
Sperical ,enveloped,spikes,80-120nm
2 copies of +ssRNA
3 structural genes :gag, pol and env
Reverse transcriptase, integrase
RNA cDNA RNA:DNA DNA:DNA
Budding release

4. Human immunodeficiency virus ( HIV )

5. According to estimates, there are now 39
According to estimates, there are now 39.5 million people living with HIV, including 2.3 million children.
Around 95% of people with HIV/AIDS live in developing nations.
Started on 1st December 1988, World AIDS Day is not just about raising money, but also about increasing awareness, fighting prejudice and improving education.
World AIDS Day is important in reminding people that HIV has not gone away, and that there are many things still to be done.

8. Pathogen of AIDS ( Acquired Immune Deficiency Syndrome ).
HIV-Ⅰ,HIV-Ⅱ

9. Biological properties
Spherical, nm, enveloped, spikes.
Structure:
Core: 2 copies of +ssRNA ( dimer ), P7
reverse transcriptase; integrase, protease,
Capsid protein: P24.
Matrix protein: P17.
Envelope: gp41 and gp120

10. HIV

14. HIV

15. gp120:
binding site for CD4 receptor of T cells.
be able to stimulate the production of neutralizing antibodies.
easy variation.
Gp41:
Membrane fusion

16. Genes:
Structural genes:
gag: coding for capsid proteins ( p17, p24, p7 )
pol: coding for protease, reverse transcriptase , integrase, RNase ,etc.
env: coding for gp120, gp41.

17. Regulatory genes:
Tat,rev,nef,vif,vpr,vpu/vpx

18. The Genome of HIV
The size of the HIV genome is similar to that of other retroviruses but it is more complex. There is no oncogene but there are extra open reading frames which do code for protein. In all 15 proteins are encoded in HIV and they are made because antibodies to them can be found in patients. These extra open reading frames are not typical of retroviruses such as RSV. These extra open reading frames give a clue to the complex lifestyle of HIV. Note that some of them are encoded in two or more exons so there will have to be multiple splice events to make the final RNA. Could these be a site for intervention in the replication of the virus?

19. Resistance: weak
56℃ 10min inactivated
Room temperature for 7 days
70% ethanol, 0.3%H2O2, 0.2%sodium hypochloride inactivation
Autoclaving or 100℃ 20min inactivation

20. Replication Adsorption:gp120 and CD4 and co-receptor(CXCR4 and CCR5)
RNA---cDNA---RNA:DNA--- dsDNA---integrated into host DNA (provirus)
Provirus DNA---RNA
progeny virus RNA
mRNA---protein progeny virion(budding release)

22. Budding Release of HIV

23. Pathogenesis & immunity
Infectious source: patients, infectious people.
Transmission pathway:
Sexual transmission;
By blood or blood products;
Vertical transmission: from mother to child.

25. Sexually transmission

26. Blood or blood component transmission

27. Drug abuser share needles

28. Medical instruments sharing

29. Medical device contaminated and not completely disinfected

30. Vertical transmission

31. Pathogenesis:
gp120 of HIV select CD4 receptor of CD4+ T cells---viruses multiply in CD4+ T cells---cell-mediated immunodeficiency---opportunistic infections and tumors occur.
Destruction of CD4+ T cells is achieved by:

32. Syncytium formation
Cytotoxic T cell lysis of infected cells
Apoptosis of infected CD4 cells
Natural killer cells
Antibody-dependent cell cytotoxicity.

35. Clinical features
Acute infection period
Asymptomatic latent state peroid
AIDS-related complex, ARC
AIDS stage characterized by
opportunistic infection
Tumor
CNS disease

39. Kaposi’s sarcoma in AIDS

40. Kaposi’s of palate

41. HERPES

43. AIDS assoc. lymphomas – most in brain

44. HIV and AIDS
With dissemination to extrapulmonary sites, Pneumocystis carinii tends to produce foci with prominent calcification, as seen in the kidney here grossly.

45. Lab diagnosis Isolation of the virus in culture
Co-cultivation of test sample with uninfected, mitogen-stimulated peripheral blood mononuclear cells. CPE---syncytia
The detection of viral components
proviral DNA or RNA
ELISA---P24
The detection of antibody to HIV antigens
ELISA---screening population
Western blot---confirming test

46. Control
1.Vaccines:
Several vaccines ( gene-engineering enveloped Ag vaccine, polypeptides vaccine, recombination vaccine ) are under trial.
Vaccine development is difficult because HIV mutates rapidly.

47. 2.Drugs:
Indinavir---inhibitor of viral protease
Lamivudine(3TC)---nucleotide analogs
AZT--- nucleotide analogs
etc……

50. HIV and AIDS Good correlation between number of HIV particles
measured by PCR and
progression to disease

51. HIV and AIDS
Viral load predicts
survival time

52. HIV and AIDS CD4 cell count is not a good predictor of
progression to disease