MAPPING OF INDEPENDENT V3 ENVELOPE DETERMINANTS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 MACROPHAGE TROPISM AND SYNCYTIUM FORMATION IN LYMPHOCYTES

The V3 region of the human immunodeficiency virus type 1 (HIV-1) envel ope protein is known to have a major influence on macrophage tropism a s well as the ability to cause syncytium formation or fusion in CD4-po sitive lymphocyte cultures. Using infectious molecular HIV-1 clones, a series of mutant clones was created which allowed detailed mapping of V3 amino acid positions involved in these properties. In these experi ments the non-syncytium-inducing phenotype in T cells did not always c orrelate with macrophage tropism. Macrophage tropism appeared to depen d on the presence of certain combinations of amino acids at five speci fic positions within and just outside of the V3 loop itself, whereas s yncytium formation in lymphocytes was influenced by substitution of pa rticular residues at two to four positions within V3. In most cases, d ifferent V3 amino acid positions were found to independently influence macrophage tropism and syncytium formation in T cells and position 13 was the only V3 location which appeared to simultaneously influence b oth macrophage tropism and syncytium formation in lymphocytes.