Tumor necrosis factor receptor expression and signal transduction in HIV-1-infected cells

S. T. Butera, B. D. Roberts, K. Leung, G. J. Nabel, T. M. Folks

    Research output: Contribution to journalArticle

    38 Scopus citations

    Abstract

    Objective: To examine the inter-relationship between HIV-1 infection and the cell surface receptors for tumor necrosis factor (TNF)-α, an immunoregulatory cytokine that can enhance HIV-1 replication. Design: Infected promyelocytic and promonocytic cells were examined because they normally express both types of TNF receptors. Methods: TNF receptor surface expression was determined by specific monoclonal antibody recognition and flow cytometry, and signal transduction was detected by gel shift analysis. HIV-1 activation and expression was quantitated by reverse transcriptase assay. Results: In the OM-10.1 promyelocytic model of chronic infection, TNF-α-induced HIV-1 expression also resulted in a substantial increase in 75 kd TNF receptor (TR75) expression although 55 kD TNF receptor (TR55) levels were not dramatically altered. A series of uninfected parental HL-60 subclones all reduced TR75 surface expression in response to TNF-α treatment. Enhanced TR75 expression on OM-10.1 cells followed the same TNF-α-dose dependency as that observed for HIV-1 production. An increase in TR75 expression was also evident during the peak of an acute HIV-1 infection of HL-60 promyelocytes. Although TR55 expression was unaltered during TNF-α-induced HIV activation, this receptor was still involved in the viral activation process. Antibody cross-linking of TR55, in the absence of exogenous TNF-α, induced maximal HIV-1 expression, an up-modulation of surface TR75, and nuclear NF-κB activity in OM-10.1 cultures. Surprisingly, this was the case even when an antagonistic anti-TR55 antibody was used. Anti-TR55 antibody cross-linking in chronically infected U1 promonocytic cultures could only partially substitute for TNF-α-induced HIV-1 expression. Conclusions: Our results demonstrated that HIV-1 infection can selectively influence the surface expression of TNF receptors, potentially influencing its own expression and altering normal immunoregulatory signal transduction.

    Original languageEnglish (US)
    Pages (from-to)911-918
    Number of pages8
    JournalAIDS
    Volume7
    Issue number7
    DOIs
    StatePublished - Jan 1 1993

    Keywords

    • Agonistic/antagonistic antibodies
    • Latent/inducible HIV-1 infection
    • NF-κB activity
    • Tumor necrosis factor receptor

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology
    • Infectious Diseases

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  • Cite this

    Butera, S. T., Roberts, B. D., Leung, K., Nabel, G. J., & Folks, T. M. (1993). Tumor necrosis factor receptor expression and signal transduction in HIV-1-infected cells. AIDS, 7(7), 911-918. https://doi.org/10.1097/00002030-199307000-00002