CRYPTIC NATURE OF ENVELOPE V3 REGION EPITOPES PROTECTS PRIMARY MONOCYTOTROPIC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 FROM ANTIBODY NEUTRALIZATION

Characterization of biological and immunological properties of human i mmunodeficiency virus type 1 (HIV-1) is critical to developing effecti ve therapies and vaccines for AIDS. With the use of a novel CD4(+) T-c ell line (PM-1) permissive to infection by both monocytotropic (MT) an d T-cell-tropic virus types, we present a comparative analysis of the immunological properties of a prototypic primary MT isolate of HIV-1 s train JR-CSF (MT-CSF) with those of a T-cell-tropic variant (T-CSF) of the same virus, which emerged spontaneously in vitro. The parental MT -CSF infected only PM-1 cells and was markedly resistant to neutraliza tion by sera from HIV-1-infected individuals, rabbit antiserum to reco mbinant MT-CSF gp120, and anti-V3 monoclonal antibodies. The T-CSF var iant infected a variety of CD4(+) T-cell lines, contained positively c harged amino acid substitutions in the gp120 V3 region, and was highly sensitive to antibody neutralization. Neutralization and antibody sta ining of T-CSF-expressing cells were significantly inhibited by HIV-1 V3 peptides; in contrast, the MT strain showed only weak V3-specific b inding of polyclonal and monoclonal antibodies. Exposure of PM-1 cells to a mixture of both viruses in the presence of human anti-HIV-1 neut ralizing antiserum resulted in infection with only MT-CSF. These resul ts demonstrate that although the V3 region of MT viruses is immunogeni c, the target epitopes in the V3 principal neutralizing domain on the membrane form of the MT envelope appear to be cryptic or hidden from b locking antibodies.