Antiviral functional divergence between two duplicated sting homeologs in amphitriploid gibel carp.

Gibel carp (Carassius gibelio) is an economically important aquaculture species, and the infection with cyprinid herpesvirus 2 (CyHV-2) can cause severe disease outbreaks and significant economic losses; however, the antiviral innate immune mechanisms in this species remain poorly understood. The stimulator of interferon (IFN) genes (STING) is a key adaptor in antiviral innate immunity and plays a central role in the induction of IFN responses. In this study, we identified and characterized two sting homeologs, sting-A and sting-B, in amphitriploid gibel carp. Although both STING proteins localize to the endoplasmic reticulum (ER) and are transcriptionally upregulated upon CyHV-2 infection, STING-A displays markedly stronger IFN-inducing activity and antiviral capacity than STING-B. Further analyses show that both homeologs are able to interact with TBK1-A and TBK1-B, but display distinct interaction patterns. Specifically, the binding of STING-B to TBK1-A and TBK1-B depends on its C-terminal CDN and CTT domains, whereas STING-A retains the ability to interact with TBK1 even after deletion of either the CDN or CTT domain. Taken together with the sequence characteristics and functional analyses, these results indicate that STING-A and STING-B have undergone functional divergence in antiviral innate immunity, which may be associated with subfunctionalization of duplicated genes following polyploidization. This study provides new insights into the functional divergence of duplicated sting genes and advances our understanding of antiviral innate immunity in gibel carp.