Ca2+ plays an antiviral role by increasing p53 expression to achieve protection against spring viraemia of carp virus infection

Calcium (Ca) is a messenger that regulates a multitude of physiological processes, but its functions in antiviral progress remain undefined. In this study, we found that Ca-2(+) enhances fish survival to defend against spring viraemia of carp virus (SVCV) infection by reversing the instability of p53 mediated by the viral protein. First, Ca-2(+) significantly protected cells and fish against SVCV infection by inducing early apoptosis. Additionally, p53 expression, which was inhibited by SVCV N protein, was upregulated by Ca-2(+) treatment. Then, the mechanism underlying the reduction of K63-linked p53 ubiquitination by SVCV N protein via the K358 site was completely prevented by Ca-2(+). These findings reveal the role of Ca-2(+) in lower vertebrates in the antiviral response, which is connected to and corresponds with viral immune evasion, providing a solution to fish diseases caused by pathogens.