Ou Jiajun, Dai Yixin, Jiang Yujie, Dai Lingzhi, Xu Liang, Lu Gang, Lou Gaoming, Li Shoujun
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Henry Fok School of Biology and Agriculture, Shaoguan University, Shaoguan, China.
Front Vet Sci. 2025 May 21;12:1560273. doi: 10.3389/fvets.2025.1560273. eCollection 2025.
Canine influenza virus (CIV) is a respiratory pathogen that causes fever, coughing, and sneezing in dogs and is continuously circulating in canine populations. Tetherin is an antiviral host restriction factor mediated by interferon, capable of inhibiting the release of enveloped viruses from infected cells. The antiviral mechanism of tetherin is mainly due to its unusual topology, which includes a short N-terminal cytoplasmic tail (CT), a transmembrane (TM) domain, a coiled-coil extra-cellular region (CC), and a C-terminal glycosyl-phosphatidylinositol anchor (GPI). Previous studies have found that canine tetherin has the ability to limit the release of CIV, but its main antiviral domain remains unclear. In the present study, the potential CT, TM, CC, and GPI domains of canine tetherin were predicted through systemic bioinformatic analysis, and mutational variants of canine tetherin based on the four domains were constructed. Confocal microscopy demonstrated that the CT, TM, and CC domains are critical for the cell membrane localization of canine tetherin. The results of CIV infection experiments showed that the TM region is a critical functional domain of canine tetherin in limiting the replication of CIV. Our study will help better understand the antiviral activity of canine tetherin and the role of the structural domains of canine tetherin in inhibiting the replication of CIV.
犬流感病毒（CIV）是一种呼吸道病原体，可导致犬类发热、咳嗽和打喷嚏，并且在犬类群体中持续传播。束缚素是一种由干扰素介导的抗病毒宿主限制因子，能够抑制包膜病毒从受感染细胞中释放。束缚素的抗病毒机制主要归因于其独特的拓扑结构，其中包括一个短的N端细胞质尾巴（CT）、一个跨膜（TM）结构域、一个卷曲螺旋细胞外区域（CC）和一个C端糖基磷脂酰肌醇锚定（GPI）。先前的研究发现犬束缚素具有限制CIV释放的能力，但其主要抗病毒结构域仍不清楚。在本研究中，通过系统的生物信息学分析预测了犬束缚素潜在的CT、TM、CC和GPI结构域，并构建了基于这四个结构域的犬束缚素突变体。共聚焦显微镜显示，CT、TM和CC结构域对于犬束缚素在细胞膜上的定位至关重要。CIV感染实验结果表明，TM区域是犬束缚素限制CIV复制的关键功能结构域。我们的研究将有助于更好地理解犬束缚素的抗病毒活性以及犬束缚素结构域在抑制CIV复制中的作用。
