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

A Simmons, V Aluvihare, A McMichael

Research output: Contribution to journalArticlepeer-review

237 Citations (Scopus)

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-CDS 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
Original languageEnglish
Pages (from-to)763 - 777
Number of pages15
JournalImmunity
Volume14
Issue number6
DOIs
Publication statusPublished - 2001

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