Seshamma T, Bagasra O, Pomerantz RJ; International Conference on AIDS.

Int Conf AIDS. 1993 Jun 6-11; 9: 179 (abstract no. PO-A14-0268).

Div. of Inf. Dis., Thomas Jefferson Univ., Philadelphia, PA.

HIV-1 infection is characterized by a prolonged variable period of clinical asymptomatic infection, sometimes lasting over 10 years. This clinically latent period may be based, in part on the development of cells which maintain HIV-1 in a state of quiescence. We and others have demonstrated models of HIV-1 proviral latency in a variety of cell culture systems and possibly in vivo. We now report on the molecular mechanisms which may be operative in latent cells in vitro, as well as in vivo. We have demonstrated that the proximal causes of proviral latency may be based on a variety of molecular mechanisms. Both the integration site of HIV-1 provirus, based on chromatin structure and/or silencing sequences within the cellular DNA flanking regions, and the intracellular milieu of transcription factors may lead to a pattern of proviral latency characterized by either no viral RNA expression or viral RNA expression characterized by a preponderance of multiply-spliced species. Further data on molecular mechanisms of a common pathway toward proviral latency will be presented. In addition utilizing in situ PCR techniques, we demonstrate reservoirs of latently-infected cells in both the peripheral bloodstream and semen of infected individuals. These techniques have been used to expand knowledge of the cell-types latently-infected with HIV-1 in HIV-1-seropositive individuals, in agreement with in situ PCR studies of the visna virus system. Finally, we have evaluated mechanisms of proviral latency in peripheral blood mononuclear cells of infected individuals and show data which suggests that proviral latency is not solely due, in vivo, to partially defective proviruses but, rather, to the intracellular environment into which the proviruses have integrated. These data will be used to suggest a variety of different forms of HIV-1 proviral latency which may be operative in certain infected individuals.

Publication Types:

• Meeting Abstracts

Keywords:

• Animals
• Base Sequence
• HIV Infections
• HIV-1
• In Vitro
• Models, Molecular
• Polymerase Chain Reaction
• Proviruses
• RNA, Viral
• Semen
• Sheep
• Transcription, Genetic
• genetics

Other ID:

• 93333699

UI: 102203073

From Meeting Abstracts