ROLE OF HIV-1 ENVELOPE V3 LOOP CLEAVAGE IN CELL TROPISM

The envelope protein is an important determinant of HIV-1 cell-specifi c tropism. The gp160 envelope precursor proteins from macrophage-tropi c or T lymphoid cell line-tropic strains of HIV-1 were expressed in re combinant vaccinia virus-infected cell lines or primary lymphocytes or macrophages. No significant differences in the kinetics of synthesis of gp160, processing into gp120 and gp41 proteins, N-linked glycosylat ion, or release of gp120 into the medium were noted with the different envelope proteins. However, gp120 envelope protein shed into the medi um was found to be at least partially cleaved at a site within the V3 loop. The gp120 envelope proteins from macrophage-tropic isolates exhi bited lower rates of cleavage than those from lymphoid cell line-tropi c strains in all cell types examined. Cell-free protease digestion stu dies also demonstrated relative resistance of the envelopes from macro phage-tropic compared to lymphoid cell line-tropic strains. All recomb inant envelope proteins were recognized by monoclonal antibodies direc ted at gp41 or the C-terminal gp120 epitopes, and no differences in bi nding to CD4 were noted.