Destruction of primary CD4+ T cells by cell-cell interaction in human immunodeficiency virus type 1 infection in vitro

Institute for Virology and Immunobiology, University of Würzburg, Versbacher Strasse 7, 97078 Würzburg, Germany 1 Author for correspondence: Christian Jassoy. Fax +49 931 201 3934. e-mail jassoy{at}vim.uni-wuerzburg.de Infection of CD4 + T lymphocytes with human immunodeficiency virus (HIV) in vitro is accompanied by extensive cytopathicity. The mechanism of cell death is unclear, but may be related to expression of the viral envelope glycoprotein. Here, it is demonstrated that T cell destruction in primary T cells occurs upon contact of infected with uninfected lymphocytes. Cell death was due to the interaction of the envelope glycoprotein with CD4 and subsequent fusion of the cells. Agents that interfered with cell-to-cell fusion such as a monoclonal antibody to CD4 and the peptide T20 prevented T cell death and depletion. In contrast, single-cell lysis due to expression and intracellular processing of the envelope glycoprotein was insignificant. These results suggest that cell-to-cell fusion and concomitant rapid cell death promote the depletion of T cells in HIV-infected individuals.