HIV-1 accessory proteins VPR and Vif modulate antiviral response by targeting IRF-3 for degradation
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231 (United States)
- University of Maryland, School of Medicine, Baltimore, MD 21231 (United States)
- Laboratory of Molecular Microbiology, National Institutes of Health, Bethesda, MD 20892 (United States)
- Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University, Baltimore, MD 21231 (United States)
The activation of IRF-3 during the early stages of viral infection is critical for the initiation of the antiviral response; however the activation of IRF-3 in HIV-1 infected cells has not yet been characterized. We demonstrate that the early steps of HIV-1 infection do not lead to the activation and nuclear translocation of IRF-3; instead, the relative levels of IRF-3 protein are decreased due to the ubiquitin-associated proteosome degradation. Addressing the molecular mechanism of this effect we show that the degradation is independent of HIV-1 replication and that virion-associated accessory proteins Vif and Vpr can independently degrade IRF-3. The null mutation of these two genes reduced the capacity of the HIV-1 virus to down modulate IRF-3 levels. The degradation was associated with Vif- and Vpr-mediated ubiquitination of IRF-3 and was independent of the activation of IRF-3. N-terminal lysine residues were shown to play a critical role in the Vif- and Vpr-mediated degradation of IRF-3. These data implicate Vif and Vpr in the disruption of the initial antiviral response and point to the need of HIV-1 to circumvent the antiviral response during the very early phase of replication.
- OSTI ID:
- 21078035
- Journal Information:
- Virology, Vol. 373, Issue 1; Other Information: DOI: 10.1016/j.virol.2007.10.042; PII: S0042-6822(07)00732-5; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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