Differential regulation of CC chemokine gene expression in human immunodeficiency virus-infected myeloid cells.
The importance of chemokine expression on HIV infection has been emphasized by the discovery that infection of CD4(+) T cells by M-tropic strains of HIV-1 is antagonized by the chemokines RANTES, MIP-1alpha, and MIP-1beta, which are natural ligands of CCR5, a major coreceptor for macrophagetropic (M-tropic) isolates of HIV-1. Similarly, the CCR2b ligands MCP-1 and MCP-3 inhibit productive infection of PBMCs by both CCR5- and CXCR4-dependent strains of HIV-1, suggesting that expression of the MCP-1 chemokine may affect HIV infection via signaling through the CCR2 receptor and subsequent desensitization of the CCR5 and/or CXCR4 signaling pathway. Given the major role played by chemokine receptors in HIV-1 fusion/entry and the regulatory effects of chemokines on HIV-1 infection, we examined the pattern of chemokine gene expression in HIV-1-infected myeloid cells and in primary monocyte/macrophages. Chronic HIV-1 infection of U937 monocytic cells increased the expression of RANTES, MIP-1alpha, MIP-1beta, and IL-8 chemokine genes, but strongly inhibited PMA/PHA- and TNFalpha-induced MCP-1 gene transcription. HIV-1-mediated inhibition of MCP-1 transcription and secretion was further confirmed in de novo HIV-1-infected U937 cells and correlated with a delay in HIV- and signal-induced NF-kappaB binding to the MCP-1 promoter. The inhibition of MCP-1 gene expression may provide a mechanism by which HIV-1 escapes the early influence of chemokine expression in monocytic cells.
Génin
P
P
Lady Davis Institute for Medical Research, McGill University, Montreal, H3T 1E2, Canada.
Mamane
Y
Y
Kwon
H
H
LePage
C
C
Wainberg
M A
MA
Hiscott
J
J
D002478:Cells, Cultured; D019742:Chemokines, CC / Q000235:genetics* / Q000276:immunology; D015967:Gene Expression Regulation, Viral / Q000276:immunology*; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007962:Leukocytes / Q000276:immunology* / Q000821:virology*
D019742:Chemokines, CC