Retrovirus

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

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

Human immunodeficiency virus ( HIV )

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.

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

Biological properties Spherical, 80-120nm, enveloped, spikes. Structure: Core: 2 copies of +ssRNA ( dimer ), P7 reverse transcriptase; integrase, protease, Capsid protein: P24. Matrix protein: P17. Envelope: gp41 and gp120

HIV

HIV

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

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.

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

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?

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

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)

Budding Release of HIV

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

Sexually transmission

Blood or blood component transmission

Drug abuser share needles

Medical instruments sharing

Medical device contaminated and not completely disinfected

Vertical transmission

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:

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

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

Kaposi’s sarcoma in AIDS

Kaposi’s of palate

HERPES

AIDS assoc. lymphomas – most in brain

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

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

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.

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

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

HIV and AIDS Viral load predicts survival time

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