Amino acid changes in the fourth conserved region of human immunodeficiency virus type 2 strain HIV-2ROD 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 binding and to influence viral tropism (A. Cordonnier, L. Montagnier, and M. Emerman, Nature [London] 340:571-574, 1989). To define the role of the corresponding region of HIV-2, we introduce single amino acid changes into the C4 sequence of HIV-2ROD. The effects of these mutations on glycoprotein function and on virus infectivity have been examined. We have shown that the tryptophan residue at position 428 is necessary primarily for CD4 binding. The isoleucine residue at position 421 is necessary for the establishment of productive infection in the promonocytic cell line U937, while it is dispensable to some extent for infection of primary T lymphocytes or the lymphocytic cell line SUP-T1. This replication defect correlated with the failure of the Ile-421-to-Thr (Ile-421-->Thr) mutant glycoprotein to form syncytia in U937 cells. DNA analysis of revertant viruses revealed that a strong selective pressure was exerted on residue 421 of the surface glycoprotein to allow HIV-2 infection of U937 cells. These results demonstrate that this region of HIV-2 plays an important role in determining fusion efficiency in a cell-dependent manner and consequently can influence viral tropism.
Unité d'Oncologie Virale (Centre National de la Recherche Scientifique UA1157), Institut Pasteur, Paris, France.
R
R
Keller
K
K
Peden
S
S
Paulous
L
L
Montagnier
A
A
Cordonnier
D000595:Amino Acid Sequence; D001483:Base Sequence; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D003062:Codon / Q000235:genetics; D017124:Conserved Sequence; D003545:Cysteine / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D015726:Giant Cells; D016325:HIV Long Terminal Repeat; D015498:HIV-2 / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008561:Membrane Fusion; D008715:Methionine / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D010641:Phenotype; D010957:Plasmids; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
D015704:CD4 Antigens; D003062:Codon; D004279:DNA, Viral; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D008715:Methionine; D001616:beta-Galactosidase; D003545:Cysteine