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PMID: 9499040 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Evidence that antibody-mediated neutralization of human immunodeficiency virus type 1 by sera from infected individuals is independent of coreceptor usage.

Journal of virology ·Vol. 72 ·No. 3 ·1998-03-00 ·Pages 1886-93

Montefiori DC, Collman RG, Fouts TR, Zhou JY, Bilska M, Hoxie JA, Moore JP, Bolognesi DP

Abstract

Human immunodeficiency virus type 1 (HIV-1) uses a variety of chemokine receptors as coreceptors for virus entry, and the ability of the virus to be neutralized by antibody may depend on which coreceptors are used. In particular, laboratory-adapted variants of the virus that use CXCR4 as a coreceptor are highly sensitive to neutralization by sera from HIV-1-infected individuals, whereas primary isolates that use CCR5 instead of, or in addition to, CXCR4 are neutralized poorly. To determine whether this dichotomy in neutralization sensitivity could be explained by differential coreceptor usage, virus neutralization by serum samples from HIV-1-infected individuals was assessed in MT-2 cells, which express CXCR4 but not CCR5, and in mitogen-stimulated human peripheral blood mononuclear cells (PBMC), where multiple coreceptors including CXCR4 and CCR5 are available for use. Our results showed that three of four primary isolates with a syncytium-inducing (SI) phenotype and that use CXCR4 and CCR5 were neutralized poorly in both MT-2 cells and PBMC. The fourth isolate, designated 89.6, was more sensitive to neutralization in MT-2 cells than in PBMC. We showed that the neutralization of 89.6 in PBMC was not improved when CCR5 was blocked by having RANTES, MIP-1alpha, and MIP-1beta in the culture medium, indicating that CCR5 usage was not responsible for the decreased sensitivity to neutralization in PBMC. Consistent with this finding, a laboratory-adapted strain of virus (IIIB) was significantly more sensitive to neutralization in CCR5-deficient PBMC (homozygous delta32-CCR5 allele) than were two of two SI primary isolates tested. The results indicate that the ability of HIV-1 to be neutralized by sera from infected individuals depends on factors other than coreceptor usage.

MeSH Terms
Cell Line, Transformed Cells, Cultured Chemokine CCL3 Chemokine CCL4 Chemokine CCL5/immunology HIV Antibodies/immunology HIV Infections/blood,immunology HIV-1/immunology Humans Leukocytes, Mononuclear/cytology,immunology Macrophage Inflammatory Proteins/immunology Middle Aged Neutralization Tests Receptors, CCR5/immunology Receptors, CXCR4/immunology
Chemicals
Chemokine CCL3 Chemokine CCL4 Chemokine CCL5 HIV Antibodies Macrophage Inflammatory Proteins Receptors, CCR5 Receptors, CXCR4
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Montefiori D C
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA. monte005@mc.duke.edu
Collman R G
Fouts T R
Zhou J Y
Bilska M
Hoxie J A
Moore J P
Bolognesi D P
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.72.3.1886-1893.1998
Email
monte005@mc.duke.edu
Published
1998-03-00
Pages
1886-93
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC109479
Subset
IM
Grants
NIAID NIH HHS · AI-35502 · United States
NIAID NIH HHS · R37 AI036082 · United States
NIAID NIH HHS · AI-28662 · United States
NIAID NIH HHS · R01 AI035502 · United States
NIAID NIH HHS · AI-15106 · United States
NIAID NIH HHS · R01 AI041420 · United States
External Links
PubMed source DOI: 10.1128/JVI.72.3.1886-1893.1998 PMC Full Text View journal details
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