Differential regulation of CC chemokine gene expression in human immunodeficiency virus-infected myeloid cells

Virology. 1999 Sep 1;261(2):205-15. doi: 10.1006/viro.1999.9852.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Chemokines, CC / genetics*
  • Chemokines, CC / immunology
  • Gene Expression Regulation, Viral / immunology*
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV-1*
  • Humans
  • Leukocytes / immunology*
  • Leukocytes / virology*

Substances

  • Chemokines, CC