Cryo-EM structure of severe fever with thrombocytopenia syndrome virus

Du，Shouwen1,2,3; Peng，Ruchao4; Xu，Wang5; Qu，Xiaoyun1,6; Wang，Yuhang2; Wang，Jiamin5; Li，Letian5; Tian，Mingyao5; Guan，Yudong2; Wang，Jigang2; Wang，Guoqing3; Li，Hao7; Deng，Lingcong5; Shi，Xiaoshuang5; Ma，Yidan5; Liu，Fengting2; Sun，Minhua1; Wei，Zhengkai1; Jin，Ningyi5; Liu，Wei7; Qi，Jianxun8,9; Liu，Quan1,3,10; Liao，Ming1,6; Li，Chang3,5

2023-12-01

10.1038/s41467-023-41804-7

Nature Communications   影响因子和分区

2041-1723

The severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne human-infecting bunyavirus, which utilizes two envelope glycoproteins, Gn and Gc, to enter host cells. However, the structure and organization of these glycoproteins on virion surface are not yet known. Here we describe the structure of SFTSV determined by single particle reconstruction, which allows mechanistic insights into bunyavirus assembly at near-atomic resolution. The SFTSV Gn and Gc proteins exist as heterodimers and further assemble into pentameric and hexameric peplomers, shielding the Gc fusion loops by both intra- and inter-heterodimer interactions. Individual peplomers are associated mainly through the ectodomains, in which the highly conserved glycans on N914 of Gc play a crucial role. This elaborate assembly stabilizes Gc in the metastable prefusion conformation and creates some cryptic epitopes that are only accessible in the intermediate states during virus entry. These findings provide an important basis for developing vaccines and therapeutic drugs.

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WOS:001095507700002

2-s2.0-85173709548

Scopus

1.Key Laboratory of Livestock Disease Prevention of Guangdong Province,Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques of Guangdong Province,Ministry of Agriculture and Rural Affairs,Institute of Animal Health,Guangdong Academy of Agricultural Sciences,Guangzhou,China
2.The First Affiliated Hospital (Shenzhen People’s Hospital),Southern University of Science and Technology,Shenzhen,China
3.Department of Infectious Diseases and Center for Infectious Diseases and Pathogen Biology,Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education,State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases,Key Laboratory for Zoonosis Research of the Ministry of Education,The First Hospital of Jilin University,Changchun,China
4.Department of Biochemistry and Biophysics,Perelman School of Medicine,University of Pennsylvania,Philadelphia,United States
5.Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses,Chinese Academy of Medical Sciences,Changchun Veterinary Research Institute,Chinese Academy of Agricultural Sciences,Changchun,China
6.Key Laboratory of Zoonosis of Ministry of Agriculture and Rural Affairs,South China Agricultural University,Guangzhou,China
7.State Key Laboratory of Pathogen and Biosecurity,Beijing Institute of Microbiology and Epidemiology,Beijing,China
8.CAS Key Laboratory of Pathogenic Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences,Beijing,China
9.Savaid Medical School,University of Chinese Academy of Sciences,Beijing,China
10.Guangdong Key Laboratory of Animal Conservation and Resource Utilization,Institute of Zoology,Guangdong Academy of Sciences,Foshan University,Foshan,China

Du，Shouwen,Peng，Ruchao,Xu，Wang,et al. Cryo-EM structure of severe fever with thrombocytopenia syndrome virus[J]. Nature Communications,2023,14(1).

Du，Shouwen.,Peng，Ruchao.,Xu，Wang.,Qu，Xiaoyun.,Wang，Yuhang.,...&Li，Chang.(2023).Cryo-EM structure of severe fever with thrombocytopenia syndrome virus.Nature Communications,14(1).

Du，Shouwen,et al."Cryo-EM structure of severe fever with thrombocytopenia syndrome virus".Nature Communications 14.1(2023).