AIDSWEEKLY Plus; Monday, November 1, 2004
Staff Medical Writers

According to recent research published in the journal Cell Death and Differentiation, "CD4+ T-cell death is a crucial feature of AIDS pathogenesis, but the mechanisms involved remain unclear.

"We present in vitro findings that identify a novel process of HIV-1 mediated killing of bystander CD4+ T cells, which does not require productive infection of these cells but depends on the presence of neighboring dying cells."

"X4-tropic HIV-1 strains, which use CD4 and CXCR4 as receptors for cell entry, caused death of unstimulated noncycling primary CD4+ T cells only if the viruses were produced by dying, productively infected T cells, but not by living, chronically infected T cells or by living HIV1-transfected HeLa cells," J.D. Lelievre and colleages.

"Inducing cell death in HIV1-transfected HeLa cells was sufficient to obtain viruses that caused CD4+ T-cell death. The addition of supernatants from dying control cells, including primary T cells," said researchers, "allowed viruses produced by living HIV-1-transfected cells to cause CD4+ T-cell death."

"CD4+ T-cell killing required HIV-1 fusion and/or entry into these cells," the authors continued, "but neither HIV1 envelope-mediated CD4 or CXCR4 signaling nor the presence of the HIV-1 Nef protein in the viral particles.

"Supernatants from dying control cells contained CD95 ligand (CD95L), and antibody-mediated neutralization of CD95L prevented these supernatants from complementing HIV-1 in inducing CD4+ T-cell death."

"Our in vitro findings suggest that the very extent of cell death induced in vivo during HIV-1 infection by either virus cytopathic effects or immune activation may by itself provide an amplification loop in AIDS pathogenesis," concluded scientists.

"More generally, they provide a paradigm for pathogen-mediated killing processes in which the extent of cell death occurring in the microenvironment might drive the capacity of the pathogen to induce further cell death."

Lelievre and colleagues published their study in Cell Death and Differentiation (A novel mechanism for HIV-1-mediated bystander CD4+T-cell death: neighboring dying cells drive the capacity of HIV1 to kill noncycling primary CD4+T cells. Cell Death Differ. 2004 Sep;11(9):1017-27.

For additional information, contact J.D. Lelievre, University Paris 07, INSERM, EMIU9922, Faculty Med Xavier Bichat, APHP, IFR02, 16 Rue Henri Huchard, F-75018 Paris, France.

The publisher's contact information for the journal Cell Death and Differentiation is: Nature Publishing Group, Macmillan Building, 4 Crinan St., London N1 9XW, England.

The information in this article comes under the major subject areas of Aids, Cd4, Cd4+t Cells, Cd95 Ligand, Cell Death, Cxcr4, Env, Hiv, Nef, Pathogenesis, and Virology.

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

Reference

Lelievre JD, Mammano F, Arnoult D, et al., "A novel mechanism for HIV1-mediated bystander CD4+ T-cell death: neighboring dying cells drive the capacity of HIV1 to kill noncycling primary CD4+ T cells", Cell Death Differ. 2004 Sep;11(9):1017-27

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