Implication for alphavirus host-cell entry and assembly indicated by a 3.5Å resolution cryo-EM structure

• Published in: Nature communications Vol. 9; no. 1; pp. 5326 - 8
• Main Authors: Chen, Lihong, Wang, Ming, Zhu, Dongjie, Sun, Zhenzhao, Ma, Jun, Wang, Jinglin, Kong, Lingfei, Wang, Shida, Liu, Zaisi, Wei, Lili, He, Yuwen, Wang, Jingfei, Zhang, Xinzheng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14-12-2018; Nature Publishing Group; Nature Portfolio
• Subjects: 101/28; 631/1647/2258/1258/1259; 631/326/596/1282; 631/326/596/2148; Alphavirus - growth & development; Animals; Assembly; Chlorocebus aethiops; Cryoelectron Microscopy - methods; Crystallography, X-Ray; Drug development; E2 protein; Heterogeneity; Humanities and Social Sciences; Hydrophobicity; Life cycle engineering; Life Cycle Stages; Life cycles; Membrane Glycoproteins - chemistry; Models, Molecular; multidisciplinary; Protein Conformation; Protein Interaction Domains and Motifs; Proteins; Residues; Ribonucleic acid; RNA; RNA viruses; Science; Science (multidisciplinary); Sindbis Virus - growth & development; Sindbis Virus - ultrastructure; Structural analysis; Vaccines; Vero Cells; Viral Envelope Proteins - chemistry; Virion - growth & development; Virion - ultrastructure; Virions; Virus Assembly; Virus Internalization; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-07704-x

Alphaviruses are enveloped RNA viruses that contain several human pathogens. Due to intrinsic heterogeneity of alphavirus particles, a high resolution structure of the virion is currently lacking. Here we provide a 3.5 Å cryo-EM structure of Sindbis virus, using block based reconstruction method that overcomes the heterogeneity problem. Our structural analysis identifies a number of conserved residues that play pivotal roles in the virus life cycle. We identify a hydrophobic pocket in the subdomain D of E2 protein that is stabilized by an unknown pocket factor near the viral membrane. Residues in the pocket are conserved in different alphaviruses. The pocket strengthens the interactions of the E1/E2 heterodimer and may facilitate virus assembly. Our study provides structural insights into alphaviruses that may inform the design of drugs and vaccines.
Alphaviruses are enveloped RNA viruses that contain several human pathogens. Here, the authors use block-based reconstruction method and provide a 3.5 Å cryo-EM structure of sindbis virus that identifies a conserved hydrophobic pocket near the viral membrane that is stabilized by an unknown pocket factor.