Functional role of the V1/V2 region of human immunodeficiency virus type 1 envelope glycoprotein gp120 in infection of primary macrophages and soluble CD4 neutralization.
We have examined the influence of the V1/V2 region of the human immunodeficiency virus type 1 (HIV-1) gp120 on certain biologic properties of the virus. We observed that on the genomic background of the T-cell-line-tropic strain, HIV-1SF2mc, both the V1 and V2 domains of the macrophage-tropic strain, HIV-1SF162mc, in addition to the required V3 domain, are necessary to attain full macrophage tropism. Furthermore, the V2 domain modulates the sensitivity of HIV-1 to soluble CD4 neutralization. Structural studies of recombinant and mutant envelope glycoproteins suggest that the function of the V1/V2 region is to interact with the V3 domain and confer on the envelope gp120 of HIV-1SF2mc a conformation more similar to that of the macrophage-tropic strain HIV-1SF162mc. The conformation of the envelope gp120 appears to be strain specific and plays an important role in determining HIV-1 tissue tropism and sensitivity to soluble CD4 neutralization.
Koito
A
A
Department of Medicine, University of California, San Francisco 94143-0128.
Harrowe
G
G
Levy
J A
JA
Cheng-Mayer
C
C
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000276:immunology*; D015686:Gene Products, env / Q000096:biosynthesis / Q000235:genetics; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000378:metabolism; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000254:growth & development* / Q000276:immunology* / Q000472:pathogenicity; D000882:Haplorhini; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics; D011995:Recombination, Genetic; D017386:Sequence Homology, Amino Acid; D014774:Virulence / Q000235:genetics; D014779:Virus Replication
D015704:CD4 Antigens; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors