TRIM33 is a member of the tripartite motif (TRIM) superfamily which contributes to regulate a multitude of cellular processes, including innate immune responses. Viperin_sv1 has recently been identified as a novel splice variant of viperin that triggers a strong antiviral effect by activating the interferon signaling pathway. SVCV infection is known to cause the degradation of viperin_sv1 through a proteasome pathway; however, the underlying mechanism remains unsolved. In this study, we identify that TRIM33 protein interacts and colocalizes with viperin_sv1 protein to induce its degradation. Additional analysis revealed that the N-terminus, but not the C-terminus, region of TRIM33 is essential for interacting with and inducing the degradation of viperin_sv1 protein. Moreover, SVCV infection enhances the expression of TRIM33 which is proved to reduce the type-1 interferon response and to promote viral replication. In conclusion, our study demonstrates that TRIM33 enhances the replication of SVCV by dampening the antiviral protein viperin_sv1 expression. These findings may lay a foundation for developing novel therapeutic strategies to halt SVCV infection.

TRIM33是三方基序（TRIM）超家族的成员，该家族有助于调节多种细胞过程，包括先天免疫应答。最近，Viperin_sv1被鉴定为一种新型的viperin剪接变体，可通过激活干扰素信号传导途径来触发强大的抗病毒作用。已知SVCV感染可通过蛋白酶体途径引起viperin_sv1的降解。但是，底层机制仍未解决。在这项研究中，我们确定TRIM33蛋白与viperin_sv1蛋白相互作用并共定位以诱导其降解。进一步的分析表明，TRIM33的N端而非C端区域对于与viperin_sv1蛋白相互作用并诱导其降解至关重要。而且，SVCV感染增强了TRIM33的表达，这被证明可以减少1型干扰素的应答并促进病毒复制。总之，我们的研究表明TRIM33通过抑制抗病毒蛋白viperin_sv1的表达增强SVCV的复制。这些发现可能为开发新的治疗策略以阻止SVCV感染奠定基础。