Cryo-EM structure of severe fever with thrombocytopenia syndrome virus.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 10 2023
10 10 2023
Historique:
received:
23
02
2023
accepted:
19
09
2023
medline:
1
11
2023
pubmed:
11
10
2023
entrez:
10
10
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37816705
doi: 10.1038/s41467-023-41804-7
pii: 10.1038/s41467-023-41804-7
pmc: PMC10564799
doi:
Substances chimiques
Viral Envelope Proteins
0
Glycoproteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6333Informations de copyright
© 2023. Springer Nature Limited.
Références
Yu, X. J. et al. Fever with thrombocytopenia associated with a novel bunyavirus in China. N. Engl. J. Med. 364, 1523–1532 (2011).
pubmed: 21410387
pmcid: 3113718
Kim, K. H. et al. Severe fever with thrombocytopenia syndrome, South Korea, 2012. Emerg. Infect. Dis. 19, 1892–1894 (2013).
pubmed: 24206586
pmcid: 3837670
Takahashi, T. et al. The first identification and retrospective study of severe fever with thrombocytopenia syndrome in Japan. J. Infect. Dis. 209, 816–827 (2014).
pubmed: 24231186
Tran, X. C. et al. Endemic severe fever with thrombocytopenia syndrome, Vietnam. Emerg. Infect. Dis. 25, 1029–1031 (2019).
pubmed: 31002059
pmcid: 6478219
Zhang, N. et al. Modelling the transmission dynamics of severe fever with thrombocytopenia syndrome in Jiangsu Province, China. Parasit Vectors 14, 237 (2021).
pubmed: 33957950
pmcid: 8100741
Jiang, X. L. et al. A cluster of person-to-person transmission cases caused by SFTS virus in Penglai, China. Clin. Microbiol. Infect. 21, 274–279 (2015).
pubmed: 25687766
Zhuang, L. et al. Transmission of severe fever with thrombocytopenia syndrome virus by Haemaphysalis longicornis ticks, China. Emerg. Infect. Dis. 24, 868–871 (2018).
pubmed: 29664718
pmcid: 5938789
Mehand, M. S., Al-Shorbaji, F., Millett, P. & Murgue, B. The WHO R&D Blueprint: 2018 review of emerging infectious diseases requiring urgent research and development efforts. Antiviral Res. 159, 63–67 (2018).
pubmed: 30261226
pmcid: 7113760
ICTV. ICTV taxonomy history: SFTS virus, https://talk.ictvonline.org/taxonomy/p/taxonomy-history?taxnode_id=20141803&src=NCBI&ictv_id=20141803 (2020).
Yuan, F. & Zheng, A. Entry of severe fever with thrombocytopenia syndrome virus. Virol. Sin. 32, 44–50 (2017).
pubmed: 27995422
Elliott R. M. & Schmaljohn C. S. Bunyaviruses. In: Knipe D. M., Howley P. M., editors. Fields Virology. 5th edition ed. Lipincott Williams & Wilkins (2013).
Lozach, P. Y. et al. DC-SIGN as a receptor for phleboviruses. Cell Host Microbe 10, 75–88 (2011).
pubmed: 21767814
Sun, Y. et al. Nonmuscle myosin heavy chain IIA is a critical factor contributing to the efficiency of early infection of severe fever with thrombocytopenia syndrome virus. J Virol 88, 237–248 (2014).
pubmed: 24155382
pmcid: 3911693
Hofmann, H. et al. Severe fever with thrombocytopenia virus glycoproteins are targeted by neutralizing antibodies and can use DC-SIGN as a receptor for pH-dependent entry into human and animal cell lines. J. Virol. 87, 4384–4394 (2013).
pubmed: 23388721
pmcid: 3624395
Freiberg, A. N., Sherman, M. B., Morais, M. C., Holbrook, M. R. & Watowich, S. J. Three-dimensional organization of Rift Valley fever virus revealed by cryoelectron tomography. J. Virol. 82, 10341–10348 (2008).
pubmed: 18715915
pmcid: 2573222
Huiskonen, J. T., Overby, A. K., Weber, F. & Grunewald, K. Electron cryo-microscopy and single-particle averaging of Rift Valley fever virus: evidence for GN-GC glycoprotein heterodimers. J. Virol. 83, 3762–3769 (2009).
pubmed: 19193794
pmcid: 2663282
Sherman, M. B., Freiberg, A. N., Holbrook, M. R. & Watowich, S. J. Single-particle cryo-electron microscopy of Rift Valley fever virus. Virology 387, 11–15 (2009).
pubmed: 19304307
Overby, A. K., Pettersson, R. F., Grunewald, K. & Huiskonen, J. T. Insights into bunyavirus architecture from electron cryotomography of Uukuniemi virus. Proc. Natl Acad. Sci. USA 105, 2375–2379 (2008).
pubmed: 18272496
pmcid: 2268144
Serris, A. et al. The hantavirus surface glycoprotein lattice and its fusion control mechanism. Cell 183, 442–456 e416 (2020).
pubmed: 32937107
pmcid: 7572791
Wu, Y. et al. Structures of phlebovirus glycoprotein Gn and identification of a neutralizing antibody epitope. Proc. Natl Acad. Sci. USA 114, E7564–E7573 (2017).
pubmed: 28827346
pmcid: 5594662
Halldorsson, S. et al. Structure of a phleboviral envelope glycoprotein reveals a consolidated model of membrane fusion. Proc. Natl Acad. Sci. USA 113, 7154–7159 (2016).
pubmed: 27325770
pmcid: 4932967
Dessau, M. & Modis, Y. Crystal structure of glycoprotein C from Rift Valley fever virus. Proc. Natl Acad. Sci. USA 110, 1696–1701 (2013).
pubmed: 23319635
pmcid: 3562824
Guardado-Calvo, P. et al. A glycerophospholipid-specific pocket in the RVFV class II fusion protein drives target membrane insertion. Science 358, 663–667 (2017).
pubmed: 29097548
Kim, K. H. et al. An anti-Gn glycoprotein antibody from a convalescent patient potently inhibits the infection of severe fever with thrombocytopenia syndrome virus. PLoS Pathog. 15, e1007375 (2019).
pubmed: 30707748
pmcid: 6380599
Guo, X. et al. Human antibody neutralizes severe fever with thrombocytopenia syndrome virus, an emerging hemorrhagic fever virus. Clin. Vaccine Immunol. 20, 1426–1432 (2013).
pubmed: 23863504
pmcid: 3889583
Moming, A. et al. Fine mapping epitope on glycoprotein-Gn from severe fever with thrombocytopenia syndrome virus. PLoS ONE 16, e0248005 (2021).
pubmed: 33651850
pmcid: 7924767
Sanchez, R. M., Zhang, Y., Chen, W., Dietrich, L. & Kudryashev, M. Subnanometer-resolution structure determination in situ by hybrid subtomogram averaging - single particle cryo-EM. Nat. Commun. 11, 3709 (2020).
pubmed: 32709843
pmcid: 7381653
Zhu, D. et al. Pushing the resolution limit by correcting the Ewald sphere effect in single-particle Cryo-EM reconstructions. Nat. Commun. 9, 1552 (2018).
pubmed: 29674632
pmcid: 5908801
Wang, Q. et al. Neutralization mechanism of human monoclonal antibodies against Rift Valley fever virus. Nat. Microbiol. 4, 1231–1241 (2019).
pubmed: 30936489
Guardado-Calvo, P. et al. Mechanistic insight into bunyavirus-induced membrane fusion from structure-function analyses of the hantavirus envelope glycoprotein Gc. PLoS Pathog. 12, e1005813 (2016).
pubmed: 27783711
pmcid: 5082683
Lescar, J. et al. The fusion glycoprotein shell of Semliki Forest virus: an icosahedral assembly primed for fusogenic activation at endosomal pH. Cell 105, 137–148 (2001).
pubmed: 11301009
Rey, F. A., Heinz, F. X., Mandl, C., Kunz, C. & Harrison, S. C. The envelope glycoprotein from tick-borne encephalitis virus at 2 A resolution. Nature 375, 291–298 (1995).
pubmed: 7753193
Kampmann, T., Mueller, D. S., Mark, A. E., Young, P. R. & Kobe, B. The role of histidine residues in low-pH-mediated viral membrane fusion. Structure 14, 1481–1487 (2006).
pubmed: 17027497
Song, H. et al. Molecular basis of arthritogenic alphavirus receptor MXRA8 binding to chikungunya virus envelope protein. Cell 177, 1714–1724 (2019).
pubmed: 31080063
Basore, K. et al. Cryo-EM structure of chikungunya virus in complex with the Mxra8 receptor. Cell 177, 1725–1737 (2019).
pubmed: 31080061
pmcid: 7227486
Mangala Prasad, V., Klose, T. & Rossmann, M. G. Assembly, maturation and three-dimensional helical structure of the teratogenic rubella virus. PLoS Pathog. 13, e1006377 (2017).
pubmed: 28575072
pmcid: 5470745
Sun, S. Y. et al. Structural analyses at pseudo atomic resolution of chikungunya virus and antibodies show mechanisms of neutralization. Elife 2, e00435 (2013).
pubmed: 23577234
pmcid: 3614025
Yuan, S. A. et al. Cryo-EM structure of a herpesvirus capsid at 3.1 angstrom. Science 360, eaao7283 (2018).
pubmed: 29622627
Dowd, K. A. & Pierson, T. C. The many faces of a dynamic virion: implications of viral breathing on flavivirus biology and immunogenicity. Annu. Rev. Virol. 5, 185–207 (2018).
pubmed: 30265634
Dai, L. et al. Structures of the Zika virus envelope protein and its complex with a flavivirus broadly protective antibody. Cell Host Microbe 19, 696–704 (2016).
pubmed: 27158114
Franca, R. et al. New anti-flavivirus fusion loop human antibodies with zika virus-neutralizing potential. Int. J. Mol. Sci. 23, https://doi.org/10.3390/ijms23147805 (2022).
Deng, Y.-Q. et al. A broadly flavivirus cross-neutralizing monoclonal antibody that recognizes a novel epitope within the fusion loop of E protein. PLoS ONE 6, e16059 (2011).
pubmed: 21264311
pmcid: 3019176
Halldorsson, S. et al. Shielding and activation of a viral membrane fusion protein. Nat. Commun. 9, 349 (2018).
pubmed: 29367607
pmcid: 5783950
Sun, Z. et al. Architecture of severe fever with thrombocytopenia syndrome virus. Protein Cell https://doi.org/10.1093/procel/pwad019 (2023).
Cheng, J., Li, B., Si, L. & Zhang, X. Determining structures in a native environment using single-particle cryoelectron microscopy images. Innovation (Camb) 2, 100166 (2021).
pubmed: 34632438
Zhang, X. et al. First fatal infection and phylodynamic analysis of severe fever with thrombocytopenia syndrome virus in Jilin province, northeastern China. Virol. Sin. 36, 329–332 (2021).
pubmed: 32458298
Reed, L. J. & Muench, H. A simple method of estimating fifty per cent endpoints. Am. J. Epidemiol. 27, 493–497 (1938).
Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).
pubmed: 28250466
pmcid: 5494038
Kremer, J. R., Mastronarde, D. N. & McIntosh, J. R. Computer visualization of three-dimensional image data using IMOD. J. Struct. Biol. 116, 71–76 (1996).
pubmed: 8742726
Himes, B. A. & Zhang, P. emClarity: software for high-resolution cryo-electron tomography and subtomogram averaging. Nat. Methods 15, 955–961 (2018).
pubmed: 30349041
pmcid: 6281437
Scheres, S. H. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519–530 (2012).
pubmed: 23000701
pmcid: 3690530
Zhang, K. Gctf: Real-time CTF determination and correction. J. Struct. Biol. 193, 1–12 (2016).
pubmed: 26592709
pmcid: 4711343
Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. Elife 7, e42166 (2018).
pubmed: 30412051
pmcid: 6250425
Kucukelbir, A., Sigworth, F. J. & Tagare, H. D. Quantifying the local resolution of cryo-EM density maps. Nat. Methods 11, 63–65 (2014).
pubmed: 24213166
Pettersen, E. F. et al. UCSF Chimera-a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).
pubmed: 15264254
Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213–221 (2010).
pubmed: 20124702
pmcid: 2815670
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486–501 (2010).
pubmed: 20383002
pmcid: 2852313
Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr. 66, 12–21 (2010).
pubmed: 20057044
Goddard, T. D. et al. UCSF ChimeraX: Meeting modern challenges in visualization and analysis. Protein Sci. 27, 14–25 (2018).
pubmed: 28710774
Humphrey, W., Dalke, A. & Schulten, K. VMD: visual molecular dynamics. J. Mol. Graph. 14, 33–38 (1996).
pubmed: 8744570
Roberts, E., Eargle, J., Wright, D. & Luthey-Schulten, Z. MultiSeq: unifying sequence and structure data for evolutionary analysis. BMC Bioinf. 7, 382 (2006).
Xu, W. et al. Transmembrane domain of IFITM3 is responsible for its interaction with influenza virus HA2 subunit. Virol. Sin. 37, 664–675 (2022).
pubmed: 35809785
pmcid: 9583175