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    Immunity. 2001 Jun;14(6):763-77.

    Nef triggers a transcriptional program in T cells imitating single-signal T cell activation and inducing HIV virulence mediators.

    Simmons A, Aluvihare V, McMichael A.

    Source

    MRC Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom.

    Abstract

    Gene expression profiling was used to explore the role of Nef in HIV. Nef induces a transcriptional program in T cells that is 97% identical to that of anti-CD3 T cell activation. This program is inhibited in the presence of cyclosporin. A requirement for TCR zeta and ZAP-70 is demonstrated for formation of the complete profile. Among eight factors particular to the anti-CD3 activation profile are IL16 and YY1, negative regulators of HIV transcription. In contrast, Nef exclusively upregulates factors positively regulating HIV, including Tat-SF1, U1 SNRNP, and IRF-2. New genes associated with Nef include CDK9, the induction of which enhances Tat function. Thus, Nef acts as a master switch early in the viral life cycle, forcing an environment conducive to dynamic viral production.

    PMID:
    11420046
    [PubMed - indexed for MEDLINE]

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