Oscillation of the human immunodeficiency virus surface receptor is regulated by the state of viral activation in a CD4+ cell model of chronic infection

S. T. Butera, V. L. Perez, B. Y. Wu, G. J. Nabel, T. M. Folks

    Research output: Contribution to journalArticlepeer-review

    130 Scopus citations

    Abstract

    We have developed a unique physiologic model of chronic human immunodeficiency virus type 1 (HIV-1) infection, OM-10.1, clonally derived from infected HL-60 promyelocytes and harboring a single integrated provirus. Unlike other models of chronic infection, OM-10.1 cultures remain CD4+ under normal culture conditions, during which <10% of the cells constitutively express HIV-1 proteins. However, when treated with tumor necrosis factor alpha (TNF-α), OM-10.1 cultures dramatically increased (>35-fold) HIV-1 expression and rapidly down-modulated surface CD4, as >95% of the cells became HIV-1+. The complete loss of surface CD4 following viral activation was neither associated with apparent cytopathicity nor due to a decline of available CD4 mRNA. There was, however, a temporal association between CD4 down-modulation and the accumulation of intracellular HIV-1 gp160/120; in addition, intracellular CD4-gp160 complexes were identifiable in OM-10.1 cell lysates at time points following TNF-α induction after surface CD4 was no longer detectable. Surface CD4 expression by OM-10.1 cells returned once viral activation ceased and could be repeatedly oscillated upon HIV-1 reactivation. Furthermore, inhibition of protein kinase activity following maximal TNF-α stimulation of OM-10.1 cells quickly returned activated HIV-1 to a state of latency, as evidenced by an accelerated return of surface CD4. These results with the new OM-10.1 cell line demonstrate that CD4 surface expression can be maintained during chronic infection and is critically dependent on the state of viral activation, that CD4-gp160 intracellular complexing is involved in CD4 down-modulation, and that protein kinase pathways not only function in the primary induction of latent HIV-1 but also are required for maintaining the state of viral activation.

    Original languageEnglish (US)
    Pages (from-to)4645-4653
    Number of pages9
    JournalJournal of virology
    Volume65
    Issue number9
    DOIs
    StatePublished - 1991

    ASJC Scopus subject areas

    • Microbiology
    • Immunology
    • Insect Science
    • Virology

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