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

Helena Schmidtmayerova, Hans S.L.M. Nottet, Gerard Nuovo, Tobias Raabe, Clinton R. Flanagan, Larisa Dubrovsky, Howard E. Gendelman, Anthony Cerami, Michael Bukrinsky, Barbara Sherry

Research output: Contribution to journalArticle

258 Scopus citations

Abstract

Two chemokine (chemoattractant cytokines) β peptides, macrophage inflammatory proteins 1α and 1β (MIP-1α and MIP-1β), 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 β peptides. In addition, HIV infection markedly altered the pattern of β chemokine expression elicited by tumor necrosis factor (TNF), itself a potent proinflammatory cytokine up-regulated 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-1α and MIP-1β 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-1α and MIP- 1β are potent chemoattractants for both monocytes and specific subpopulations of lymphocytes, this dysregulation of β 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.

Original languageEnglish (US)
Pages (from-to)700-704
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number2
DOIs
StatePublished - Jan 23 1996

ASJC Scopus subject areas

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