AEGiS-13IAC: HIV envelope induces virus expression in the HIV-infected resting CD4+ T cell reservoir without inducing cellular activation or apoptosis.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

HIV envelope induces virus expression in the HIV-infected resting CD4+ T cell reservoir without inducing cellular activation or apoptosis.

Int Conf AIDS 2000 Jul 9-14; 13:38 (abstract no.. LbPeA7024)

Kinter A, Umscheid C, Arthos J, Cicala C, Chun TW, Ehler L, White A, Jackson R, Donoghue E, Fauci A
National Institutes of Health, Bethesda, MD 20892. Fax: 301-402-4122, E-mail: akinter@niaid.nih.gov.

BACKGROUND: Resting CD4+ T (RT4) cells are a well characterized cellular HIV reservoir believed to play an important role in the persistence of HIV in vivo following long-term HAART. It is not clear whether this cellular HIV reservoir contributes to the low level viral replication demonstrated to occur in many HAART treated patients, including those with plasma viremia of <50 copies/ml. We have investigated the potential of various physiologic factors to activate or to induce cell death in RT4 cells. In the present study, we investigate the effects of HIV envelope gp160 on HIV expression and on cellular activation/apoptosis in this cellular reservoir of HIV.

METHODS: RT4 (CD25-,HLA DR-) cells were isolated and exposed to soluble trimeric gp160. Supernatants were tested by p24 and bDNA assay for HIV production and for infectivity of virus. Cells were tested for activation markers, cell signaling events and for apoptosis by TUNEL assay.

RESULTS: Gp160 from both R5 and X4 HIV strains induced variable levels of HIV expression from RT4 cells and this virus was infectious. Induction of HIV expression was not associated with expression of activation markers (CD25, CD69 or HLA DR), thymidine uptake or induction of apoptosis. Gp160s from both R5 and X4 HIV strains induced phosphorylation of p56 Ick and ZAP70; however, only R5 gp160s stimulated calcium flux through chemokine receptors.

CONCLUSIONS: These data suggest that the interaction of RT4 cells with HIV envelope may be one mechanism through which the infected resting CD4+ T cell population can express virus while avoiding activation-induced apoptosis, thus maintaining a stable HIV reservoir.

Keywords: AEGIS, Antigens, CD4, HIV Infections, T-Lymphocytes, Apoptosis, CD4-Positive T-Lymphocytes, HIV-1, Virus Replication, Antiretroviral Therapy, Highly Active, HIV Seropositivity, Receptors, Interleukin-2, Viruses, Human, immunology, virology, AIDS
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