Open AccessKeap1 recognizes EIAV early accessory protein Rev to promote antiviral defense
Author(s) -
Yan Wang,
Guanqin Ma,
Xuefeng Wang,
Na Lei,
Xing Guo,
Jiaqi Zhang,
Cong Liu,
Cheng Du,
Tingxiang Qi,
Yuezhi Lin,
Xiaojun Wang
Publication year - 2022
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009986
Subject(s) - keap1 , psychological repression , biology , virology , viral replication , virus , immune system , transcription factor , microbiology and biotechnology , lentivirus , gene , genetics , gene expression , viral disease
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.