Keap1 recognizes EIAV early accessory protein Rev to promote antiviral defense.
PLoS Pathog
; 18(2): e1009986, 2022 02.
Article
in En
| MEDLINE
| ID: mdl-35139135
ABSTRACT
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.
Full text:
1
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Gene Products, rev
/
Infectious Anemia Virus, Equine
/
Kelch-Like ECH-Associated Protein 1
Limits:
Humans
Language:
En
Year:
2022
Type:
Article