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PMID: 9576751 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Blockade of CC chemokine receptor 5 (CCR5)-tropic human immunodeficiency virus-1 replication in human lymphoid tissue by CC chemokines.

The Journal of clinical investigation ·Vol. 101 ·No. 9 ·1998-05-01 ·Pages 1876-80

Margolis LB, Glushakova S, Grivel JC, Murphy PM

Abstract

The CC chemokines MIP-1alpha, MIP-1beta, and RANTES suppress replication of certain HIV-1 strains in cultured PBMC and T cell lines by blocking interaction of gp120 with CC chemokine receptor 5 (CCR5). However, the same chemokines can enhance HIV-1 replication in cultured macrophages. The net effect of chemokines on HIV-1 infection in intact lymphoid tissue, the major reservoir of HIV-1 in vivo, is unknown and unpredictable since the tissue contains both T lymphocytes and macrophages. Here we show that exogenous MIP-1alpha, MIP-1beta, and RANTES markedly suppressed replication of CCR5-tropic HIV-1 strains in blocks of human lymphoid tissue infected ex vivo. Moreover, endogenous MIP-1alpha, MIP-1beta, and RANTES were upregulated in tissues infected ex vivo with CXC chemokine receptor 4-tropic but not CCR5-tropic HIV-1. Such an upregulation may contribute to the virus phenotype shift in the course of HIV disease in vivo.

MeSH Terms
Chemokine CCL3 Chemokine CCL4 Chemokine CCL5/pharmacology Chemokines, CC/pharmacology Culture Techniques/methods HIV-1/drug effects Humans Lymph Nodes/virology Lymphoid Tissue/virology Macrophage Inflammatory Proteins/pharmacology Palatine Tonsil/virology Receptors, CCR5/drug effects Receptors, CXCR4/drug effects
Chemicals
Chemokine CCL3 Chemokine CCL4 Chemokine CCL5 Chemokines, CC Macrophage Inflammatory Proteins Receptors, CCR5 Receptors, CXCR4
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Margolis L B
Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Glushakova S
Grivel J C
Murphy P M
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI2015
Published
1998-05-01
Pages
1876-80
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508773
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI2015 PMC Full Text View journal details
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