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PMID: 11160708 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Increased neutralization sensitivity of CD4-independent human immunodeficiency virus variants.

Journal of virology ·Vol. 75 ·No. 5 ·2001-03-00 ·Pages 2041-50

Kolchinsky P, Kiprilov E, Sodroski J

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.

MeSH Terms
Amino Acid Sequence CD4 Antigens/metabolism,pharmacology Cell Line Giant Cells/physiology HIV Antibodies/immunology,metabolism HIV Envelope Protein gp120/chemistry,metabolism HIV-1/genetics,immunology,metabolism Humans Ligands Molecular Sequence Data Neutralization Tests Receptors, CCR5/metabolism Recombinant Proteins/pharmacology Transfection Virus Shedding
Chemicals
CD4 Antigens HIV Antibodies HIV Envelope Protein gp120 Ligands Receptors, CCR5 Recombinant Proteins recombinant soluble CD4
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kolchinsky P
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Kiprilov E
Sodroski J
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.75.5.2041-2050.2001
Published
2001-03-00
Pages
2041-50
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC114788
Subset
IM
Grants
NIAID NIH HHS · R37 AI024755 · United States
NIAID NIH HHS · P30 AI028691 · United States
NIAID NIH HHS · R01 AI041851 · United States
NIAID NIH HHS · AI31783 · United States
NIAID NIH HHS · R01 AI031783 · United States
NIAID NIH HHS · AI41851 · United States
NIAID NIH HHS · AI24755 · United States
External Links
PubMed source DOI: 10.1128/JVI.75.5.2041-2050.2001 PMC Full Text View journal details
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