Seneca Valley virus 3C protease targets the Nrf2/HO-1 pathway to antagonize its antiviral activity

Nrf2 is a crucial redox regulator responsible for initiating the expression of downstream antioxidant genes, including HO-1 and superoxide dismutase. HO-1, an enzyme induced by stress, performs protective roles through the conversion of heme into carbon monoxide, biliverdin, and iron. Nevertheless, the function of Nrf2/HO-1 during Seneca Valley virus (SVV) infection is yet to be clearly defined. In this study, we showed that SVV infection led to a reduction in the expression of Nrf2/HO-1, and the overexpression of Nrf2/HO-1 induced a potent anti-SVV effect. SVV 3C proteinase promoted the caspase-dependent degradation of Nrf2/HO-1. As a result, it attenuated the cell's ability to resist oxidative stress and counteracted the antiviral function of Nrf2/HO-1. Our research further uncovered a novel mechanism through which SVV eludes the host's antiviral effects by disrupting cellular redox balance, offering important targets for preventing and controlling SVV infection.