HUMAN-IMMUNODEFICIENCY-VIRUS ENVELOPE V1 AND V2 REGIONS INFLUENCE REPLICATION EFFICIENCY IN MACROPHAGES BY AFFECTING VIRUS SPREAD

The vs hypervariable region of the HIV-I envelope protein is a major d eterminant of viral tropism for macrophages. However, the replication of macrophage-tropic HIV-1 strains varies considerably in macrophages, and this variability has been linked to the V1 and V2 envelope region s. In the present study, recombinant HIV clones were generated by inse rting V1 and V2 sequences from the Ba-L HIV isolate, which has a high macrophage replication level, into the genomic background of a macroph age-tropic clone with a low macrophage replication level. Infection of macrophages with varying multiplicities of infection and direct detec tion of the number of infected macrophages per culture showed that the Ba-L V1 and V2 envelope sequences enhanced the ability of virus to sp read in the cultures. In contrast, macrophage-tropic clones with low r eplication efficiency infected macrophages initially but showed no evi dence of spread to additional cells during the culture period. This ef fect on virus spread appeared to be macrophage-specific as it was not observed in cultures of T lymphocytes. Comparison of recombinant clone s containing V1, V2, and vs envelope sequences from high-efficiency Ba -L and JR-FL strains indicated that markedly different V1 and V2 seque nces could impart the same rapidly spreading phenotype in macrophages. (C) 1995 Academic Press, Inc.