GP120S DERIVED FROM 4 SYNCYTIUM-INDUCING HIV-1 STRAINS INDUCE DIFFERENT PATTERNS OF CD4 ASSOCIATION WITH LYMPHOCYTE SURFACE MOLECULES

This work extends our previous finding that lymphocyte treatment with gp120(IIIB) specifically induces CD4 association with several surface molecules to other molecules and to three other gp120s from different HIV-1 strains. The ability to induce this association was displayed by the four gp120s employed, i.e. gp120(IIIB), gp120(SF2), gp120(MN), an d gp120(451), and the association patterns were different, as shown by both co-capping and immunoprecipitation. Go-capping showed that all f our gp120s significantly potentiated CD4 association with CD3, CD45RA, CD45RB, CD38, CD26, CD59 and class I MHC molecules. By contrast, CD4 association with CD95 was induced only by gp120(451) and gp120(MN); th at with CD11a only by gp120(SF2) and gp120(MN); and that with CD27 and CD45RO only by gp120(MN) and gp120(451) respectively. All gp120s indu ced significant CD4 association with CD49d, but gp120(SF2) displayed a significantly weaker effect than gp120(IIIB) Induction of association was not mediated by inside-out signaling via the CD4-associated tyros ine kinase p56(lck), since it was not inhibited by the tyrosine kinase inhibitors herbymicin and genistein, nor by CD45 bridging between CD4 and the associating molecule, since similar patterns of association w ere detected in cells expressing different CD45 isoform patterns. More over, it was not mediated by chemokine receptors interacting with the gp120 V3 loop, since RANTES did not alter the gp120-induced CD4 associ ation pattern. By contrast, the observation that gp120s from four HIV- 1 strains induce different CD4 association patterns suggests that gp12 0 directly interacts with the associating molecules, possibly via thei r hypervariable regions.