Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein

Abstract

Formation of syncytia, with progression to cell death, is a characteristic feature of in vitro cultures of susceptible cells infected with human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV)1–3. Viral antigen-positive multi-nucleated giant cells have also been observed in histological sections from infected individuals4,5. In vitro, formation of these multinucleated giant cells occurs through cell fusion which is dependent on cell-surface expression of the differentiation antigen CD4 (ref. 1). Utilizing a recombinant vaccinia virus containing the gene for the envelope glycoprotein of HTLV-III/LAV6, we demonstrate that cell-surface expression of this protein, in the absence of other HTLV-III/LAV structural or regulatory proteins, is sufficient to induce CD4-dependent cell fusion, leading to cell death, one of the characteristic manifestations of AIDS (acquired immune deficiency syndrome) virus cytopathology. This process may contribute to the loss of CD4+ T cells seen in AIDS.