Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
School of Life Sciences, University of Chinese Academy of Sciences, Beijing 101408, China.
Proc Natl Acad Sci U S A. 2017 Oct 17;114(42):E8905-E8912. doi: 10.1073/pnas.1706125114. Epub 2017 Oct 4.
Thogotoviruses are emerging tick-borne zoonotic orthomyxoviruses infecting both humans and domestic animals with severe clinical consequences. These viruses utilize a single-envelope glycoprotein (Gp) to facilitate their entry into host cells. Here, we present the Gp structures of Thogoto and Dhori viruses, both of which are members of the genus in the family These structures, determined in the postfusion conformation, identified them as class III viral fusion proteins. It is intriguing that the Gp structures are similar to the envelope protein of baculovirus, although sharing a low sequence identity of ∼28%. Detailed structural and phylogenic analyses demonstrated that these Gps originated from a common ancestor. Among the structures, domain I is the most conserved region, particularly the fusion loops. Domain II showed the highest variability among different viruses, which might be related to their distinct host tropism. These findings increase our understanding of the divergent evolution processes of various orthomyxoviruses and indicate potential targets for developing antiviral therapeutics by intercepting virus entry.
Thogotoviruses 是新兴的蜱传动物源性正粘病毒，可感染人类和家畜，导致严重的临床后果。这些病毒利用单一包膜糖蛋白（Gp）促进其进入宿主细胞。在这里，我们展示了 Thogoto 和 Dhori 病毒的 Gp 结构，它们均属于 科 的 属。这些结构在融合后构象中确定，将它们鉴定为 III 类病毒融合蛋白。有趣的是，尽管 Gp 结构与杆状病毒的包膜蛋白具有相似性，但其序列同一性约为 28%。详细的结构和系统发育分析表明，这些 Gp 起源于一个共同的祖先。在这些结构中，结构域 I 是最保守的区域，特别是融合环。结构域 II 在不同病毒之间表现出最高的变异性，这可能与其不同的宿主嗜性有关。这些发现增加了我们对各种正粘病毒的不同进化过程的理解，并表明通过阻断病毒进入可能成为开发抗病毒治疗的潜在靶点。
