Differential regulation of cellular tropism and sensitivity to soluble CD4 neutralization by the envelope gp120 of human immunodeficiency virus type 1.
Using recombinant and mutant viruses generated between two human immunodeficiency virus type 1 isolates that display differences in cell tropism and sensitivity to soluble CD4 neutralization, we show that these two properties of the virus are regulated by different mechanisms. Whereas there is an association between V3 loop conformation and a particular cellular tropism, soluble CD4 neutralization sensitivity appears to be determined by amino acid differences in the C2 domain of the envelope gp120 that modulate the stability of gp120-gp41 association. Our findings further illustrate the importance of functional interactions among different regions of the envelope gp120 in regulating the biological phenotypes of human immunodeficiency virus and suggest that additional probing of the V3 loop with monoclonal antibodies may identify specific structural features of this loop that determine cell tropism.
Cancer Research Institute, School of Medicine, University of California, San Francisco 94143-0128.
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Stamatatos
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Werner
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Cheng-Mayer
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000494:pharmacology*; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000502:physiology*; D015700:HIV Envelope Protein gp41 / Q000502:physiology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology*; D010641:Phenotype; D011487:Protein Conformation; D012995:Solubility; D014162:Transfection
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments