The KSHV immediate-early transcription factor RTA encodes ubiquitin E3 ligase activity that targets IRF7 for proteosome-mediated degradation

Yanxing Yu, Shizhen Emily Wang, Gary S. Hayward

Research output: Contribution to journalArticlepeer-review

Abstract

Many viruses encode proteins that counteract the development of the interferon (IFN)-mediated antiviral state. Here, we report that interferon regulatory factor 7 (IRF7), a key mediator of type I IFN induction, is targeted for degradation by binding to the RTA immediate-early nuclear transcription factor encoded by Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8). Cotransfection with RTA blocked IRF7-mediated IFNα and IFNβ mRNA production and promoted the ubiquitination and degradation of IRF7 protein in a proteasome-dependent fashion. Addition of RTA also promoted polyubiquitination of IRF7 in an in vitro cell free assay, demonstrating that RTA itself acts as a ubiquitin E3 ligase. RTA also autoregulated its own polyubiquitination and stability, and both activities were abolished by point mutations in a Cys plus His-rich N-terminal domain. Therefore, manipulation of the stability and function of IRF7 by the KSHV RTA transcription factor provides an unexpected regulatory strategy for circumventing the innate immune defence system.

Original languageEnglish (US)
Pages (from-to)59-70
Number of pages12
JournalImmunity
Volume22
Issue number1
DOIs
StatePublished - Jan 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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