AIDSWEEKLY Plus; Monday, July 4, 2005
Staff Medical Writers

"Apoptosis of uninfected bystander T cells contributes to T-cell depletion during human immunodeficiency virus type 1 (HIV-1) infection. HIV-1 envelope/receptor interactions and immune activation have been implicated as contributors to bystander apoptosis.

"To better understand the relationship between T-cell activation and bystander apoptosis during HIV-1 pathogenesis, we investigated the effects of the highly cytopathic CXCR4-tropic HIV-1 variant ELI6 on primary CD4+ and CD8+ T cells," scientists in the United States report.

"Infection of primary T-cell cultures with EL16 induced CD4+ T-cell depletion by direct cell lysis and bystander apoptosis. Exposure of primary CD4+ and CD8+ T cells to nonreplicating ELI6 virions induced bystander apoptosis through a Fas-independent mechanism. Bystander apoptosis of CD4+ T cells required direct contact with virions and Env/CXCR4 binding.

"In contrast," wrote G.H. Holm and colleagues at the Dana Farber Cancer Institute, "the apoptosis of CD8+ T cells was triggered by a soluble factor(s) secreted by CD4+ T cells. HIV-1 virions activated CD4+ and CD8+ T cells to express CD25 and HLA-DR and preferentially induced apoptosis in CD25+HLA-DR+ T cells in a CXCR4-dependent manner."

"Maximal levels of binding, activation, and apoptosis were induced by virions that incorporated MHC class II and B7-2 into the viral membrane," the authors said.

Holm concluded, "These results suggest that nonreplicating HIV-1 virions contribute to chronic immune activation and T-cell depletion during HIV-1 pathogenesis by activating CD4+ and CD8+ T cells, which then proceed to die via apoptosis.

"This mechanism may represent a viral immune evasion strategy to increase viral replication by activating target cells while killing immune effector cells that are not productively infected."

Holm and colleagues published their study in the Journal of Virology (Distinct mechanisms of CD4+ and CD8+ T-cell activation and bystander apoptosis induced by human immunodeficiency virus type 1 virions. J Virol. 2005 May;79(10):6299-311.

For more information, contact D. Gabuzda, Dana Farber Cancer Institute, Dept. Cancer Immunology & AIDS, JFB 816, 44 Binney St., Boston, MA 02115, USA.

Publisher contact information for the Journal of Virology is: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA.

Keywords: Boston, Massachusetts, United States, HIV/AIDS, Apoptosis, CD4+/CD8+ T Cells, Viral Replication, T-Cell Activation.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Holm GH, Gabuzda D. Distinct mechanisms of CD4+ and CD8+ T-cell activation and bystander apoptosis induced by human immunodeficiency virus type 1 virions, J Virol. 2005 May;79(10):6299-311.

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