Blockade of CC Chemokine Receptor 5 (CCR5)-tropic Human Immunodeficiency virus-1 Replication in Human Lymphoid Tissue by CC Chemokines

J Clin Invest. 1998 May 1;101(9):1876-80. doi: 10.1172/JCI2015.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

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

Substances

  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokines, CC
  • Macrophage Inflammatory Proteins
  • Receptors, CCR5
  • Receptors, CXCR4