title: Increased neutralization sensitivity of CD4-independent human immunodeficiency virus variants.
abstract: Naturally occurring human immunodeficiency virus (HIV-1) variants require the presence of CD4 and specific chemokine receptors to enter a cell. In the laboratory, HIV-1 variants that are capable of bypassing CD4 and utilizing only the CCR5 chemokine receptor for virus entry have been generated. Here we report that these CD4-independent viruses are significantly more sensitive to neutralization by soluble CD4 and a variety of antibodies. The same amino acid changes in the HIV-1 gp120 envelope glycoprotein determined CD4 independence and neutralization sensitivity. The CD4-independent envelope glycoproteins exhibited higher affinity for antibodies against CD4-induced gp120 epitopes but not other neutralizing ligands. The CD4-independent envelope glycoproteins did not exhibit increased lability relative to the wild-type envelope glycoproteins. The utilization of two receptors apparently allows HIV-1 to maintain a more neutralization-resistant state prior to engaging CD4 on the target cell, explaining the rarity of CD4 independence in wild-type HIV-1.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kolchinsky
authors.forename: E
authors.initials: E
authors.lastname: Kiprilov
authors.forename: J
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D000595:Amino Acid Sequence; D015704:CD4 Antigens / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D015726:Giant Cells / Q000502:physiology; D015483:HIV Antibodies / Q000276:immunology* / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D019713:Receptors, CCR5 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection; D017201:Virus Shedding
chemical_list: D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D008024:Ligands; D019713:Receptors, CCR5; D011994:Recombinant Proteins; C076613:recombinant soluble CD4