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Inhibition of Human Immunodeficiency Virus Envelope Glycoprotein- Mediated Single Cell Lysis by Low-Molecular-Weight Antagonists of Viral Entry

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115,¹ Department of Pathology, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115,² Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115,³ Department of Biochemical Immunology, Merck & Co., Inc., Rahway, New Jersey 07065⁴

Received 25 May 2006/ Accepted 17 August 2006

The coexpression of human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins and receptors leads to the lysis of single cells by a process that is dependent upon membrane fusion. This cell lysis was inhibited by low-molecular-weight compounds that interfere with receptor binding or with receptor-induced conformational transitions in the envelope glycoproteins. A peptide, T20, potently inhibited cell-cell fusion but had no effect on single cell lysis mediated by the HIV-1 envelope glycoproteins. Thus, critical events in the lysis of single cells by the HIV-1 envelope glycoproteins occur in intracellular compartments accessible only to small inhibitory compounds.

Published ahead of print on 30 August 2006.