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NLM AIDSLINE

Membrane-expressed HIV envelope glycoprotein heterodimer is a powerful inducer of cell death in uninfected CD4+ target cells.




 

Res Virol. 1995 Jan-Feb;146(1):5-17. Unique Identifier : AIDSLINE

HIV infection of CD4+ T cells in culture results in the production of virus and induction of cell killing by apoptosis. Such a cytopathic effect is observed during infection with syncytium-inducing or non-syncytium-inducing HIV isolates. Apoptosis is triggered by the interaction of the cell membrane-expressed HIV envelope glycoprotein heterodimer gp120-gp41 complex (external and transmembrane glycoprotein complex) with the CD4 receptor. Here we demonstrate an experimental model for the induction of apoptosis independent of HIV infection, using transiently transfected HeLa cells with the HIV1 env gene as effector cells and the CD4+ MOLT4-T4 T cells as target cells. Results obtained confirm that the induction of apoptosis requires the membrane expression of the two HIV env gene products, gp120 and gp41. Single amino acid point mutations of the envelope products that affect binding to the CD4 receptor or the fusion process abrogate the capacity of the gp120-gp41 complex to induce apoptosis. Interestingly, a point mutation in the V3 loop which inhibits fusion without affecting CD4 binding also results in the abrogation of apoptosis. These observations indicate that the induction of apoptosis is an intrinsic property of the cell membrane-expressed gp120-gp41 complex, and thus should be considered as one of the functions of HIV env gene products.

Cell Death Cell Line Cell Membrane/METABOLISM Cytopathogenic Effect, Viral *CD4-Positive T-Lymphocytes Gene Expression Regulation, Viral Genes, env Hela Cells Human HIV/*PHYSIOLOGY HIV Envelope Protein gp120/*PHYSIOLOGY HIV Envelope Protein gp41/*PHYSIOLOGY Protein Conformation Protein Precursors Support, Non-U.S. Gov't Transfection JOURNAL ARTICLE



 




Information in this article was accurate in August 30, 1995. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.