FUSION FROM WITHOUT DIRECTED BY HUMAN-IMMUNODEFICIENCY-VIRUS PARTICLES

Fusion from without is the process through which particles of some env eloped viruses can direct fusion of target cells in the absence of vir al replication. We demonstrate here that human immunodeficiency virus (HIV) particles can efficiently promote fusion from without. Using HeL a-CD4 cells carrying a Tat-inducible lacZ gene, we observed syncytia a s early as 6 h after exposure to HIV particles, before HIV gene expres sion could be detected. Efficient syncytium formation could be obtaine d when cells were treated with zidovudine, which prevented HIV replica tion and expression but not cell-cell fusion. Fusion was also observed when cells were exposed to particles of a replication-defective HIV i ntegrase mutant. Fusion from without by HIV particles could be blocked by a monoclonal antibody specific for the V3 loop of the HIV-1 envelo pe glycoprotein and by soluble CD4. This mechanism of cytopathicity, w hich can involve cells that do not actively replicate HIV and can be d irected by replication-defective particles, could participate in the p athogenicity of the CD4 cell depletion that chatacterizes HIV infectio n.