HIV-1 CYTOPATHOGENICITY-GENETIC DIFFERENCE BETWEEN DIRECT CYTOTOXIC AND FUSOGENIC EFFECT

Formation of large syncytia, rapid cell killing, and early onset of replication are characteristics of the highly cytopathic Zairian virus strain HIV1 NDK compared with the HIV1 LAV prototype. Recombinant provirus molecules derived from cloned infectious DNAs of HIV1 LAV and NDK were constructed by reciprocal exchange of genetic material using conserved restriction sites. Different regions of the HIV1 genome were responsible for variability of the direct single-cell cytotoxic and fusogenic effects. A minimal, provisionally defined portion of genetic information responsible for the higher cytotoxicity of HIV1 NDK compared to the HIV1 LAV prototype was localized in the fragment Spel1042 EcoRIl483, containing the 3′-terminal half of gag and a majority of the pol gene. This region also determined the rapid replication properties of HIV1 NDK. The increased fusogenic potential of HIVI NDK was associated with the simultaneous presence of HIV1 NDK fragments BssHII255 SpeI1042 and EcoRI5278 XhoI8401, which contained the splicing donor, packaging sequence, pl8 gag protein, and the HIV env gene. The increase in the direct killing effect but not in the syncytium forming ability of HIVI NDK correlated with the early onset of replication and rapid spread of HIV1 NDK in cell cultures. The HIV1 NDK fragments BssHII SpeI and EcoRI XhoI were by themselves necessary but not sufficient to induce formation of large syncytia. © 1992.