Human cytomegalovirus-stimulated peripheral blood mononuclear cells induce HIV-1 replication via a tumor necrosis factor-α-mediated mechanism

Phillip K. Peterson, Genya Gekker, Chun C. Chao, Shuxian Hu, Charlene Edelman, Henry H Balfour, Jan Verhoef

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Abstract

Human cytomegalovirus (HCMV) is a potential cofactor in HIV-1 infection. To investigate the mechanism whereby HCMV promotes HIV-1 replication, a PBMC coculture assay which measures HIV-1 p24 antigen release was used as an index of viral replication. HCMV-stimulated PBMC were capable of inducing HIV-1 replication in cocultures with acutely infected PBMC; however, this occurred only when the PBMC were from HCMV-seropositive donors (598±207 versus 27±10 pg/ml p24 antigen with PBMC from HCMV-seronegative donors on day 6 of coculture). Upon stimulation with HCMV, PBMC obtained exclusively from HCMV-seropositive donors released tumor necrosis factor (TNF)-α (270±79 pg/ml at 18 h of culture). Monoclonal antibodies to TNF-α blocked the activity of HCMV-stimulated PBMC in cocultures both with acutely HIV-1-infected PBMC and with the chronically infected promonocytic line U1. Also, treatment of HCMV-stimulated PBMC with pentoxifylline, an inhibitor of TNF-α mRNA, markedly reduced HIV-1 replication in cocultures both with acutely and chronically infected cells. These results indicate that TNF-α is a key mediator of HIV-1 replication induced by HCMV-stimulated PBMC and support the concept that this cytokine plays an important role in the pathogenesis of HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)574-580
Number of pages7
JournalJournal of Clinical Investigation
Volume89
Issue number2
DOIs
StatePublished - 1992

Keywords

  • AIDS
  • Cytokines
  • Interleukins
  • Pentoxifylline
  • Viral infection

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