AN ENVELOPE MODIFICATION THAT RENDERS A PRIMARY, NEUTRALIZATION-RESISTANT CLADE-B HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATE HIGHLY SUSCEPTIBLE TO NEUTRALIZATION BY SERA FROM OTHER CLADES

SF162 is a primary (PR), non-syncytium-inducing, macrophagetropic huma n immunodeficiency virus type 1 (HIV-1) clade B isolate which is resis tant to antibody-mediated neutralization. Deletion of the first or sec ond hypervariable envelope gp120 region (V1 or V2 loop, respectively) of this virus does not abrogate its ability to replicate in peripheral blood mononuclear cells and primary macrophages, nor does it alter it s coreceptor usage profile. The mutant virus with the V1 loop deletion , SF162 Delta V1, remains as resistant to antibody-mediated neutraliza tion as the wild-type virus SF162, In contrast, the mutant virus with the V2 loop deletion, SF162 Delta V2, exhibits enhanced susceptibility to neutralization by certain monoclonal antibodies whose epitopes are located within the CD4-binding site and conserved regions of gp120. M ore importantly, SF162 Delta V2 is now up to 170-fold more susceptible to neutralization than SF162 by sera collected from patients infected with clade B HIV-1 isolates. In addition, it becomes susceptible to n eutralization by sera collected from patients infected with clade A, C , D, E, and F HIV-1 isolates. These findings suggest that the V2, but not the V1, loop of SF162 shields an as yet unidentified region of the HIV envelope rich in neutralization epitopes and that the overall str ucture of this region appears to be conserved among clade B, C, D, E, and F HIV-1 PR isolates.