HIV replication in CD4+ T cells of HIV-infected individuals is regulated by a balance between the viral suppressive effects of endogenous β-chemokines and the viral inductive effects of other endogenous cytokines

Audrey L. Kinter, Mario Ostrowski, Delia Goletti, Alessandra Oliva, Drew Weissman, Kira Gantt, Elena Hardy, Robert Jackson, Linda Ehler, Anthony S. Fauci

Research output: Contribution to journalArticle

Abstract

This study demonstrates that the β-chemokines macrophage inflammatory proteins 1α and 1β (MIP-1α and MIP-1β) and, RANTES (regulated on activation, normally T-cell expressed and secreted) inhibit human immunodeficiency virus (HIV) replication in anti-CD3 or recall antigen-stimulated peripheral blood mononuclear cells (PB-MCs) of asymptomatic HIV-infected subjects. Significant levels of β-chemokines were produced by both CD4+ and CD8+ PBMC subsets from HIV-infected individuals. Neutralization of endogenous MIP-1α, MIP-1β, and RANTES did not rescue HIV replication in cultures to which greater than 10% CD8+ T cells had been added, indicating that the HIV suppressor activity of CD8+ T cells cannot be explained entirely by the β-chemokines. However, significant enhancement of viral replication was observed upon neutralization of endogenous β-chemokines in CD8-depleted or CD4+ PBMCs from most donors, particularly in cultures with low inducible levels of HIV production. In contrast, certain endogenous proinflammatory cytokines induced HIV replication in these same cells. These data suggest that the levels of HIV replication in CD4+ PBMC reflect the balance of the opposing effects of endogenous suppressive factors, such as the β-chemokines, and HIV-inducing cytokines, such as tumor necrosis factor α and interleukin 1β.

Original languageEnglish
Pages (from-to)14076-14081
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number24
Publication statusPublished - Nov 26 1996

Keywords

  • Proinflammatory
  • Regulation

ASJC Scopus subject areas

  • General
  • Genetics

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