HIV-1 accessory proteins VPR and Vif modulate antiviral response by targeting IRF-3 for degradation

@article{citeulike:2545584, abstract = {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.}, author = {Okumura, Atsushi and Alce, Tim and Lubyova, Barbora and Ezelle, Heather and Strebel, Klaus and Pitha, Paula M. }, citeulike-article-id = {2545584}, doi = {http://dx.doi.org/10.1016/j.virol.2007.10.042}, journal = {Virology}, keywords = {apobec, hiv, innate, vpr}, month = {March}, number = {1}, pages = {85--97}, posted-at = {2008-03-17 11:35:41}, priority = {2}, title = {HIV-1 accessory proteins VPR and Vif modulate antiviral response by targeting IRF-3 for degradation}, url = {http://dx.doi.org/10.1016/j.virol.2007.10.042}, volume = {373}, year = {2008} }

TY - JOUR ID - citeulike:2545584 L3 - citeulike-article-id:2545584 TI - HIV-1 accessory proteins VPR and Vif modulate antiviral response by targeting IRF-3 for degradation JF - Virology VL - 373 IS - 1 SP - 85 EP - 97 N2 - 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. KW - apobec KW - hiv KW - innate KW - vpr AU - Okumura, Atsushi AU - Alce, Tim AU - Lubyova, Barbora AU - Ezelle, Heather AU - Strebel, Klaus AU - Pitha, Paula PY - 2008/03/30/ UR - http://dx.doi.org/10.1016/j.virol.2007.10.042 ER -