DIFFERENTIAL REGULATION OF CELLULAR TROPISM AND SENSITIVITY TO SOLUBLE CD4 NEUTRALIZATION BY THE ENVELOPE GP120 OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

Using recombinant and mutant viruses generated between two human immun odeficiency virus type 1 isolates that display differences in cell tro pism and sensitivity to soluble CD4 neutralization, we show that these two properties of the virus are regulated by different mechanisms. Wh ereas there is an association between V3 loop conformation and a parti cular cellular tropism, soluble CD4 neutralization sensitivity appears to be determined by amino acid differences in the C2 domain of the en velope gp120 that modulate the stability of gp120-gp41 association. Ou r findings further illustrate the importance of functional interaction s among different regions of the envelope gp120 in regulating the biol ogical phenotypes of human immunodeficiency virus and suggest that add itional probing of the V3 loop with monoclonal antibodies may identify specific structural features of this loop that determine cell tropism .