AMINO-ACID CHANGES IN THE 4TH CONSERVED REGION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 STRAIN HIV-2(ROD) ENVELOPE GLYCOPROTEIN MODULATE FUSION

The fourth conserved region (C4) of human immunodeficiency virus type 1 (HIV-1) surface glycoprotein has been shown to participate in CD4 bi nding and to influence viral tropism (A. Cordonnier, L. Montagnier, an d M. Emerman, Nature [London] 340:571-574, 1989). To define the role o f the corresponding region of HIV-2, we introduced single amino acid c hanges into the C4 sequence of HIV-2ROD. The effects of these mutation s on glycoprotein function and on virus infectivity have been examined . We have shown that the tryptophan residue at position 428 is necessa ry primarily for CD4 binding. The isoleucine residue at position 421 i s necessary for the establishment of productive infection in the promo nocytic cell line U937, while it is dispensable to some extent for inf ection of primary T lymphocytes or the lymphocytic cell line SUP-T1. T his replication defect correlated with the failure of the Ile-421-to-T hr (Ile-421-Thr) mutant glycoprotein to form syncytia in U937 cells. D NA analysis of revertant viruses revealed that a strong selective pres sure was exerted on residue 421 of the surface glycoprotein to allow H IV-2 infection of U937 cells. These results demonstrate that this regi on of HIV-2 plays an important role in determining fusion efficiency i n a cell-dependent manner and consequently can influence viral tropism .