STRUCTURE-FUNCTION-RELATIONSHIPS OF THE HIV-1 ENVELOPE V3 LOOP TROPISM DETERMINANT - EVIDENCE FOR 2 DISTINCT CONFORMATIONS

Objective: The V3 loop of the HIV-1 envelope glycoprotein gp120 is an important determinant of HIV-1-specific cell tropism. Nine different p urified envelope proteins were prepared in order to examine the associ ation between the structure of the gp120 proteins and functional prope rties of HIV-1 virions differing in their tropism for T-cell lines and macrophages. Results: Six monoclonal antibodies to the V3 loop reacte d preferentially with T-cell line-tropic gp120 envelope proteins, and one monoclonal antibody reacted preferentially with macrophage-tropic gp120 envelope proteins. T-cell line-tropic gp120 envelope proteins we re at least 10-fold more susceptible to V3 loop proteolytic cleavage b y human thrombin, and 1000-fold more susceptible to V3 loop proteolyti c cleavage by human mast cell tryptase than macrophage-tropic gp120 en velope proteins. Conclusions: These findings suggest that there are tw o distinct conformations for the V3 loop of T-cell line-tropic and mac rophage-tropic gp120 envelope proteins.