Loss of N-linked glycans in the V3-loop region of gp120 is correlated to an enhanced infectivity of HIV-1

We describe mutants of human immunodeficiency virus type-1 (HIV-1) strain N L4-3, which are lacking the thirteenth, fifteenth, or seventeenth sites for N-linked glycosylation (g13, g15, g17) of the envelope protein gp120, All three sites are located within the hypervariable V3 loop region of gp120, T hose mutants lacking carbohydrates g15 or combinations of g15/g17 showed ma rkedly higher infectivity for GHOST cells (human osteosarcoma cells) expres sing CXCR4 (GHOST-X4), compared to the fully glycosylated NL4-3 wild type v irus. In addition, these mutants could also infect cells which exhibits low background expression of CXCR4 corresponding to <10% of that observed for GHOST-X4 cells. In addition to the enhanced infectivity observed, mutants l acking g15 and g17 showed increased resistance to inhibition by SDF-1, the natural ligand of CXCR4. Thus, loss of the oligosaccharides g15 and g17 in the V3 region of gp120 markedly influences CXCR4-specific infection.