Tobacco mosaic virus hijacks its coat protein interacting protein IP-L to inhibit NbCML30, a novel calmodulin-like protein, to enhance its infection.

Calcium is an important plant immune signal that is essential for activating host resistance, but how RNA viruses manipulate calcium signals to promote their infections remains largely unknown. Here, we demonstrated that tobacco mosaic virus (TMV) coat protein (CP) interacting protein L (IP-L) associates with calmodulin-like protein 30 (NbCML30) in cytoplasm and nucleus, and can suppress its expression at nucleic acid and protein levels. NbCML30, which lacks the EF-Hand conserved domain and cannot bind to Ca2+ , was located at cytoplasm and nucleus and was down-regulated by TMV infection. NbCML30 silencing promoted TMV infection, while its overexpression inhibited TMV infection by activating Ca2+ -dependent oxidative stress in plants. NbCML30-mediated resistance to TMV mainly depends on IP-L regulation as the facilitation of TMV infection by silencing NbCML30 was cancelled by co-silencing NbCML30 and IP-L. Overall, these findings expand our understanding that in the absence of any reported silencing suppressor activity, TMV CP manipulates IP-L to inhibit NbCML30, influencing its Ca2+ -dependent oxidative stress activation. These results lay a theoretical foundation that will enable us to engineer tobacco with improved TMV resistance in the future.