Mathew P, Badley A, McElhinny J, Leibson P, Paya CV; National Conference on Human Retroviruses and Related Infections.
Program Abstr Second Natl Conf Hum Retrovir Relat Infect Natl Conf Hum Retrovir Relat Infect 2nd 1995 Wash DC. 1995 Jan 29-Feb 2; 135.
Mayo Clinic, Rochester, MN.
The major reservoir for persistent viral replication in human immunodeficiency virus (HIV)-infected individuals is the monocyte-macrophage system. The promonocytic U937 cell line provides a model for the understanding of viral persistence. U937 cells infected with HIV undergo apoptotic cell death, but surviving populations show continued viral replication. While bcl-2 is known to inhibit apoptosis and function as an anti-oxidant molecule, intracellular oxidative mechanisms activate HIV replication. In Epstein- Barr virus (EBV)-infected B cells, HIV has been indirectly associated with decreased bcl-2 expression via the downregulation of EBV proteins. In this study, we analyzed the expression of bcl-2 in HIV-infected monocytic cells in relationship to HIV-induced cell death and viral persistence. Within 5 days post-infection, bcl-2 protein levels decrease, and this correlates with cell death. By different methods we determined that HIV-mediated U937 death is due to apoptosis. Surviving U937 cells exhibit persistent viral replication as assayed by reverse transcriptase and p24 ELISA, and in this population, decreased bcl-2 expression is maintained. Our studies demonstrate that 1) HIV can, in the absence of interaction with other viruses, modulate bcl-2 expression; and 2) decreased bcl-2 expression is associated with apoptotic cell death and subsequent viral persistence in U937 cells. Whether manipulation of bcl-2 expression in U937 cells can modulate apoptosis or viral persistence is currently being explored.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Apoptosis
- Cell Line
- Down-Regulation
- Gene Expression
- HIV
- HIV Core Protein p24
- HIV Infections
- HIV Long Terminal Repeat
- HIV Protease
- HIV Seropositivity
- Humans
- Monocytes
- U937 Cells
- genetics
- immunology
Other ID:
UI: 102213417
From Meeting Abstracts