Keap1 recognizes EIAV early accessory protein Rev to promote antiviral defense.

Yan Wang, Guanqin Ma, Xue-Feng Wang, Lei Na, Xing Guo, Jiaqi Zhang, Cong Liu, Cheng Du, Ting Qi, Yuezhi Lin, Xiaojun Wang

PLoS pathogens 2022 Feb

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The Nrf2/Keap1 axis plays a complex role in viral susceptibility, virus-associated inflammation and immune regulation in host cells. However, whether or how the Nrf2/Keap1 axis is involved in the interactions between equine lentiviruses and their hosts remains unclear. Here, we demonstrate that the Nrf2/Keap1 axis was activated during EIAV infection. Mechanistically, EIAV-Rev competitively binds to Keap1 and releases Nrf2 from Keap1-mediated repression, leading to the accumulation of Nrf2 in the nucleus and promoting Nrf2 responsive genes transcription. Subsequently, we demonstrated that the Nrf2/Keap1 axis represses EIAV replication via two independent molecular mechanisms: directly increasing antioxidant enzymes to promote effective cellular resistance against EIAV infection, and repression of Rev-mediated RNA transport through direct interaction between Keap1 and Rev. Together, these data suggest that activation of the Nrf2/Keap1 axis mediates a passive defensive response to combat EIAV infection. The Nrf2/Keap1 axis could be a potential target for developing strategies for combating EIAV infection.

Citation

Yan Wang, Guanqin Ma, Xue-Feng Wang, Lei Na, Xing Guo, Jiaqi Zhang, Cong Liu, Cheng Du, Ting Qi, Yuezhi Lin, Xiaojun Wang. Keap1 recognizes EIAV early accessory protein Rev to promote antiviral defense. PLoS pathogens. 2022 Feb;18(2):e1009986