PDCoV NS6 and TRIM28

Porcine deltacoronavirus (PDCoV) causes a significant threat to the global swine industry. The PDCoV accessory protein NS6 has the capability to antagonize type I interferon (IFN-I) production and influence viral proliferation. In this study, we discovered that tripartite motif-containing 28 (TRIM28) interacts with NS6 via its RING and coiled-coil (CC) domains, facilitating K48-linked ubiquitination of NS6 at lysine residue K17. This ubiquitination process leads to the degradation of NS6, thereby inhibiting viral replication. Furthermore, NS6 attenuates the expression of interferon-stimulated genes (ISGs). The inhibition of the interferon (IFN) response is further intensified when the degradation of NS6 is inhibited. This study identifies TRIM28 as an antiviral factor that exerts its effects by promoting the degradation of NS6, thereby inhibiting PDCoV replication.猪德尔塔冠状病毒（Porcine deltacoronavirus, PDCoV）对全球养猪业构成严重威胁。该病毒的辅助蛋白NS6能够拮抗I型干扰素（type I interferon, IFN-I）的产生，并影响病毒增殖。本研究发现，含三联基序蛋白28（tripartite motif-containing 28, TRIM28）可通过其环指（RING）结构域与卷曲螺旋（CC）结构域与NS6发生相互作用，介导NS6在赖氨酸残基K17位点发生K48连接的泛素化修饰。该泛素化过程会引发NS6的降解，从而抑制病毒复制。此外，NS6可减弱干扰素刺激基因（interferon-stimulated genes, ISGs）的表达；当NS6的降解被抑制时，干扰素应答的抑制效应会进一步增强。本研究证实TRIM28是一种抗病毒因子，其通过促进NS6的降解发挥作用，进而抑制PDCoV的复制。