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

Leonid B. Margolis, Svetlana Glushakova, Jean-Charles B. Grivel, Philip M. Murphy

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45 Citations (Scopus)

Abstract

The CC chemokines MIP-1α, MIP-1β, 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- 1α, MIP-1β, and RANTES markedly suppressed replication of CCR5-tropic HIV- 1 strains in blocks of human lymphoid tissue infected ex vivo. Moreover, endogenous MIP-1α, MIP-1β, 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.

Original languageEnglish
Pages (from-to)1876-1880
Number of pages5
JournalJournal of Clinical Investigation
Volume101
Issue number9
Publication statusPublished - 1 May 1998
Externally publishedYes

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Keywords

  • AIDS
  • Chemokine
  • HIV
  • Leukocyte
  • Receptor

ASJC Scopus subject areas

  • Medicine(all)

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