英国格拉斯哥大学Joe Grove研究小组发现，糖蛋白结构的绘制揭示黄病毒科的演化历史。这一研究成果于2024年9月4日在线发表在国际学术期刊《自然》上。

研究人员结合系统发育分析和蛋白质结构预测，揭示了整个黄病毒科的糖蛋白。研究人员发现大多数物种，包括高度分化的jingmenviruses和大基因组黄病毒，具有与正黄病毒E糖蛋白同源的II类融合系统。然而，丙型肝炎病毒、匹基病毒和瘟病毒的E1E2糖蛋白在结构上独特，可能代表一种新型的融合机制，并严格与脊椎动物宿主感染相关。

通过将糖蛋白分布映射到系统发育树上，研究人员揭示了复杂的演化历史，标志着细菌基因的捕获和潜在的属间重组。这些通过蛋白质结构预测获得的见解，细化了人们对病毒融合机制的理解，并揭示了塑造黄病毒科多样性及其生态的关键事件。

据悉，包膜病毒中的糖蛋白驱动膜融合，并决定宿主范围、组织嗜性和致病性。尽管糖蛋白在病毒中具有重要作用，但对黄病毒科内的糖蛋白仍缺乏全面理解。黄病毒科是一个庞大的病毒家族，包括丙型肝炎、登革热和寨卡病毒等病原体，以及其他人类、动物和新兴病毒。对于许多黄病毒来说，糖蛋白尚未被鉴定，对于其他病毒，如丙型肝炎病毒，其膜融合的分子机制仍未明晰。

附：英文原文

Title: Mapping glycoprotein structure reveals Flaviviridae evolutionary history

Author: Mifsud, Jonathon C. O., Lytras, Spyros, Oliver, Michael R., Toon, Kamilla, Costa, Vincenzo A., Holmes, Edward C., Grove, Joe

Issue&Volume: 2024-09-04

Abstract: Viral glycoproteins drive membrane fusion in enveloped viruses and determine host range, tissue tropism and pathogenesis1. Despite their importance, there is a fragmentary understanding of glycoproteins within the Flaviviridae2, a large virus family that include pathogens such as hepatitis C, dengue and Zika viruses, and numerous other human, animal and emergent viruses. For many flaviviruses the glycoproteins have not yet been identified, for others, such as the hepaciviruses, the molecular mechanisms of membrane fusion remain uncharacterized3. Here we combine phylogenetic analyses with protein structure prediction to survey glycoproteins across the entire Flaviviridae. We find class II fusion systems, homologous to the Orthoflavivirus E glycoprotein in most species, including highly divergent jingmenviruses and large genome flaviviruses. However, the E1E2 glycoproteins of the hepaciviruses, pegiviruses and pestiviruses are structurally distinct, may represent a novel class of fusion mechanism, and are strictly associated with infection of vertebrate hosts. By mapping glycoprotein distribution onto the underlying phylogeny, we reveal a complex evolutionary history marked by the capture of bacterial genes and potentially inter-genus recombination. These insights, made possible through protein structure prediction, refine our understanding of viral fusion mechanisms and reveal the events that have shaped the diverse virology and ecology of the Flaviviridae. Combined phylogenetic analyses and glycoprotein structure prediction across the Flaviviridae reveals divergent membrane fusion systems and provides insights into the complex evolutionary history within this family of viruses.

DOI: 10.1038/s41586-024-07899-8

Source: https://www.nature.com/articles/s41586-024-07899-8