Blockade of CC chemokine receptor 5 (CCR5)-tropic human immunodeficiency virus-1 replication in human lymphoid tissue by CC chemokines.
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.
Margolis
L B
LB
Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Glushakova
S
S
Grivel
J C
JC
Murphy
P M
PM
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology; D019742:Chemokines, CC / Q000494:pharmacology*; D046508:Culture Techniques / Q000379:methods; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008198:Lymph Nodes / Q000821:virology; D008221:Lymphoid Tissue / Q000821:virology*; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D014066:Palatine Tonsil / Q000821:virology; D019713:Receptors, CCR5 / Q000187:drug effects*; D019718:Receptors, CXCR4 / Q000187:drug effects
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4