Human immunodeficiency virus type 1 infection alters chemokine beta peptide expression in human monocytes: implications for recruitment of leukocytes into brain and lymph nodes

Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):700-4. doi: 10.1073/pnas.93.2.700.

Abstract

Two chemokine (chemoattractant cytokines) beta peptides, macrophage inflammatory proteins 1 alpha and 1 beta (MIP-1 alpha and MIP-1 beta), were induced in human monocyte cultures following infection with the human immunodeficiency virus type 1 (HIV-1). Induction depended on productive viral infection: not only did the kinetics of MIP-1 peptide induction closely follow those of viral replication, but monocyte cultures inoculated with heat-inactivated virus or infected in the presence of AZT failed to produce these chemokine beta peptides. In addition, HIV infection markedly altered the pattern of beta chemokine expression elicited by tumor necrosis factor (TNF), itself a potent proinflammatory cytokine upregulated during the development of AIDS. Reverse transcription (RT)-PCR and RT-in situ PCR studies on brain tissue from patients with AIDS dementia demonstrated elevated MIP-1 alpha and MIP-1 beta mRNA expression relative to comparable samples from HIV-1-infected patients without dementia. Cells expressing chemokines in HIV-1-infected brains were identified morphologically as microglia and astrocytes. As MIP-1 alpha and MIP-1 beta are potent chemoattractants for both monocytes and specific subpopulations of lymphocytes, this dysregulation of beta chemokine expression may influence the trafficking of leukocytes during HIV infection. These data, taken together, suggest a mechanism by which HIV-1-infected monocytes might recruit uninfected T cells and monocytes to sites of active viral replication or inflammation, notably the brain and lymph nodes.

Publication types

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

MeSH terms

  • AIDS Dementia Complex / metabolism
  • Base Sequence
  • Brain / cytology
  • Brain / metabolism
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemotaxis, Leukocyte
  • HIV Infections / metabolism*
  • HIV-1 / growth & development*
  • Humans
  • Lymph Nodes / cytology
  • Lymph Nodes / metabolism
  • Macrophage Inflammatory Proteins
  • Molecular Sequence Data
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • Monocytes / virology
  • Monokines / biosynthesis*
  • Monokines / genetics
  • RNA, Messenger / analysis
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation*

Substances

  • Chemokine CCL3
  • Chemokine CCL4
  • Macrophage Inflammatory Proteins
  • Monokines
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha