The cryo-EM structure of homotetrameric attachment glycoprotein from langya henipavirus.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 Jan 2024
27 Jan 2024
Historique:
received:
07
07
2023
accepted:
18
01
2024
medline:
28
1
2024
pubmed:
28
1
2024
entrez:
27
1
2024
Statut:
epublish
Résumé
Langya Henipavirus (LayV) infection is an emerging zoonotic disease that has been causing respiratory symptoms in China since 2019. For virus entry, LayV's genome encodes the fusion protein F and the attachment glycoprotein G. However, the structural and functional information regarding LayV-G remains unclear. In this study, we revealed that LayV-G cannot bind to the receptors found in other HNVs, such as ephrin B2/B3, and it shows different antigenicity from HeV-G and NiV-G. Furthermore, we determined the near full-length structure of LayV-G, which displays a distinct mushroom-shaped configuration, distinguishing it from other attachment glycoproteins of HNV. The stalk and transmembrane regions resemble the stem and root of mushroom and four downward-tilted head domains as mushroom cap potentially interact with the F protein and influence membrane fusion process. Our findings enhance the understanding of emerging HNVs that cause human diseases through zoonotic transmission and provide implication for LayV related vaccine development.
Identifiants
pubmed: 38280880
doi: 10.1038/s41467-024-45202-5
pii: 10.1038/s41467-024-45202-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
812Informations de copyright
© 2024. The Author(s).
Références
Eaton, B. T., Broder, C. C., Middleton, D. & Wang, L. F. Hendra and Nipah viruses: different and dangerous. Nat. Rev. Microbiol. 4, 23–35 (2006).
pubmed: 16357858
pmcid: 7097447
doi: 10.1038/nrmicro1323
Field, H. et al. The natural history of Hendra and Nipah viruses. Microbes. Infect. 3, 307–314 (2001).
pubmed: 11334748
doi: 10.1016/S1286-4579(01)01384-3
Weatherman, S., Feldmann, H. & de Wit, E. Transmission of henipaviruses. Curr. Opin. Virol. 28, 7–11 (2018).
pubmed: 29035743
doi: 10.1016/j.coviro.2017.09.004
Madera, S. et al. Discovery and Genomic Characterization of a Novel Henipavirus, Angavokely Virus, from Fruit Bats in Madagascar. J. Virol. 96, e0092122 (2022).
pubmed: 36040175
doi: 10.1128/jvi.00921-22
Zhang, X. A. et al. A Zoonotic Henipavirus in Febrile Patients in China. N. Engl J. Med. 387, 470–472 (2022).
pubmed: 35921459
doi: 10.1056/NEJMc2202705
Mallapaty, S. New ‘Langya’ virus identified in China: what scientists know so far. Nature 608, 656–657 (2022).
pubmed: 35953571
doi: 10.1038/d41586-022-02175-z
Choudhary, O. P., Priyanka, Fahrni, M. L., Metwally, A. A. & Saied, A. A. Spillover zoonotic ‘Langya virus’: is it a matter of concern? Vet. Q. 42, 172–174 (2022).
pubmed: 36001038
pmcid: 9448363
doi: 10.1080/01652176.2022.2117874
Sanchez, S. & Ly, H. Langya henipavirus: Is it a potential cause for public health concern? Virulence 14, 2154188 (2023).
pubmed: 36599832
pmcid: 9815250
doi: 10.1080/21505594.2022.2154188
Kummer, S. & Kranz, D. C. Henipaviruses-A constant threat to livestock and humans. PLoS Negl. Trop. Dis. 16, e0010157 (2022).
pubmed: 35180217
pmcid: 8856525
doi: 10.1371/journal.pntd.0010157
Ellwanger, J. H. & Chies, J. A. B. Zoonotic spillover: Understanding basic aspects for better prevention. Genet Mol. Biol. 44, e20200355 (2021).
pubmed: 34096963
pmcid: 8182890
doi: 10.1590/1678-4685-gmb-2020-0355
Porotto, M. et al. Inhibition of Nipah virus infection in vivo: targeting an early stage of paramyxovirus fusion activation during viral entry. PLoS Pathog. 6, e1001168 (2010).
pubmed: 21060819
pmcid: 2965769
doi: 10.1371/journal.ppat.1001168
Lamb, R. A., Paterson, R. G. & Jardetzky, T. S. Paramyxovirus membrane fusion: lessons from the F and HN atomic structures. Virology 344, 30–37 (2006).
pubmed: 16364733
doi: 10.1016/j.virol.2005.09.007
Lamb, R. A. & Jardetzky, T. S. Structural basis of viral invasion: lessons from paramyxovirus F. Curr. Opin. Struct. Biol. 17, 427–436 (2007).
pubmed: 17870467
pmcid: 2086805
doi: 10.1016/j.sbi.2007.08.016
Bose, S., Jardetzky, T. S. & Lamb, R. A. Timing is everything: Fine-tuned molecular machines orchestrate paramyxovirus entry. Virology 479–480, 518–531 (2015).
pubmed: 25771804
doi: 10.1016/j.virol.2015.02.037
Dang, H. V. et al. Broadly neutralizing antibody cocktails targeting Nipah virus and Hendra virus fusion glycoproteins. Nat. Struct. Mol. Biol. 28, 426–434 (2021).
pubmed: 33927387
doi: 10.1038/s41594-021-00584-8
Xu, K. et al. Crystal structure of the Hendra virus attachment G glycoprotein bound to a potent cross-reactive neutralizing human monoclonal antibody. PLoS Pathog. 9, e1003684 (2013).
pubmed: 24130486
pmcid: 3795035
doi: 10.1371/journal.ppat.1003684
Dang, H. V. et al. An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections. Nat. Struct. Mol. Biol. 26, 980–987 (2019).
pubmed: 31570878
pmcid: 6858553
doi: 10.1038/s41594-019-0308-9
Avanzato, V. A. et al. A structural basis for antibody-mediated neutralization of Nipah virus reveals a site of vulnerability at the fusion glycoprotein apex. Proc. Natl Acad. Sci. USA 116, 25057–25067 (2019).
pubmed: 31767754
pmcid: 6911215
doi: 10.1073/pnas.1912503116
Aguilar, H. C. & Iorio, R. M. Henipavirus membrane fusion and viral entry. Curr. Top. Microbiol. Immunol. 359, 79–94 (2012).
pubmed: 22427111
Yuan, P. et al. Structural studies of the parainfluenza virus 5 hemagglutinin-neuraminidase tetramer in complex with its receptor, sialyllactose. Structure 13, 803–815 (2005).
pubmed: 15893670
doi: 10.1016/j.str.2005.02.019
Yuan, P. et al. Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk. Proc. Natl Acad. Sci. USA 108, 14920–14925 (2011).
pubmed: 21873198
pmcid: 3169104
doi: 10.1073/pnas.1111691108
Welch, B. D. et al. Structure of the parainfluenza virus 5 (PIV5) hemagglutinin-neuraminidase (HN) ectodomain. PLoS Pathog. 9, e1003534 (2013).
pubmed: 23950713
pmcid: 3738495
doi: 10.1371/journal.ppat.1003534
Wang, Z. et al. Architecture and antigenicity of the Nipah virus attachment glycoprotein. Science 375, 1373–1378 (2022).
pubmed: 35239409
doi: 10.1126/science.abm5561
Kalbermatter, D. et al. Structure and supramolecular organization of the canine distemper virus attachment glycoprotein. Proc. Natl Acad. Sci. USA 120, e2208866120 (2023).
pubmed: 36716368
pmcid: 9963377
doi: 10.1073/pnas.2208866120
Rissanen, I. et al. Idiosyncratic Mojiang virus attachment glycoprotein directs a host-cell entry pathway distinct from genetically related henipaviruses. Nat. Commun. 8, 16060, https://doi.org/10.1038/ncomms16060 (2017).
doi: 10.1038/ncomms16060
pubmed: 28699636
pmcid: 5510225
Bowden, T. A. et al. Structural basis of Nipah and Hendra virus attachment to their cell-surface receptor ephrin-B2. Nat. Struct. Mol. Biol. 15, 567–572 (2008).
pubmed: 18488039
doi: 10.1038/nsmb.1435
Xu, K. et al. Host cell recognition by the henipaviruses: crystal structures of the Nipah G attachment glycoprotein and its complex with ephrin-B3. Proc. Natl Acad. Sci. USA 105, 9953–9958 (2008).
pubmed: 18632560
pmcid: 2474567
doi: 10.1073/pnas.0804797105
Bowden, T. A. et al. Crystal structure and carbohydrate analysis of Nipah virus attachment glycoprotein: a template for antiviral and vaccine design. J. Virol. 82, 11628–11636 (2008).
pubmed: 18815311
pmcid: 2583688
doi: 10.1128/JVI.01344-08
Lee, B. et al. Molecular recognition of human ephrinB2 cell surface receptor by an emergent African henipavirus. Proc. Natl Acad. Sci. USA 112, E2156–E2165 (2015).
pubmed: 25825759
pmcid: 4418902
Laing, E. D. et al. Structural and functional analyses reveal promiscuous and species specific use of ephrin receptors by Cedar virus. Proc. Natl Acad. Sci. USA 116, 20707–20715 (2019).
pubmed: 31548390
pmcid: 6789926
doi: 10.1073/pnas.1911773116
Pernet, O., Wang, Y. E. & Lee, B. Henipavirus receptor usage and tropism. Curr. Top. Microbiol. Immunol. 359, 59–78 (2012).
pubmed: 22695915
pmcid: 3587688
Negrete, O. A. et al. EphrinB2 is the entry receptor for Nipah virus, an emergent deadly paramyxovirus. Nature 436, 401–405 (2005).
pubmed: 16007075
doi: 10.1038/nature03838
Bonaparte, M. I. et al. Ephrin-B2 ligand is a functional receptor for Hendra virus and Nipah virus. Proc. Natl Acad. Sci. USA 102, 10652–10657 (2005).
pubmed: 15998730
pmcid: 1169237
doi: 10.1073/pnas.0504887102
Negrete, O. A. et al. Two key residues in ephrinB3 are critical for its use as an alternative receptor for Nipah virus. PLoS Pathog. 2, e7 (2006).
pubmed: 16477309
pmcid: 1361355
doi: 10.1371/journal.ppat.0020007
Doyle, M. P. et al. Cooperativity mediated by rationally selected combinations of human monoclonal antibodies targeting the henipavirus receptor binding protein. Cell Rep. 36, 109628 (2021).
pubmed: 34469726
pmcid: 8527959
doi: 10.1016/j.celrep.2021.109628
May, A. J., Pothula, K. R., Janowska, K. & Acharya, P. Structures of Langya Virus Fusion Protein Ectodomain in Pre- and Postfusion Conformation. J. Virol. 97, e0043323 (2023).
pubmed: 37278642
doi: 10.1128/jvi.00433-23
Drexler, J. F. et al. Bats host major mammalian paramyxoviruses. Nat. Commun. 3, 796, https://doi.org/10.1038/ncomms1796 (2012).
doi: 10.1038/ncomms1796
pubmed: 22531181
de Souza, W. M. et al. Paramyxoviruses from neotropical bats suggest a novel genus and nephrotropism. Infect. Genet. Evol. 95, 105041 (2021).
pubmed: 34411742
doi: 10.1016/j.meegid.2021.105041
Mohd-Qawiem, F. et al. Paramyxoviruses in rodents: A review. Open Vet. J. 12, 868–876 (2022).
pubmed: 36650879
pmcid: 9805762
Wu, Z. et al. Novel Henipa-like virus, Mojiang Paramyxovirus, in rats, China, 2012. Emerg. Infect. Dis. 20, 1064–1066 (2014).
pubmed: 24865545
pmcid: 4036791
doi: 10.3201/eid2006.131022
Isaacs, A. et al. Structure and antigenicity of divergent Henipavirus fusion glycoproteins. Nat. Commun. 14, 3577 (2023).
pubmed: 37328468
pmcid: 10275869
doi: 10.1038/s41467-023-39278-8
Bowden, T. A., Crispin, M., Harvey, D. J., Jones, E. Y. & Stuart, D. I. Dimeric architecture of the Hendra virus attachment glycoprotein: evidence for a conserved mode of assembly. J. Virol. 84, 6208–6217 (2010).
pubmed: 20375167
pmcid: 2876662
doi: 10.1128/JVI.00317-10
Bradel-Tretheway, B. G., Liu, Q., Stone, J. A., McInally, S. & Aguilar, H. C. Novel Functions of Hendra Virus G N-Glycans and Comparisons to Nipah Virus. J. Virol. 89, 7235–7247 (2015).
pubmed: 25948743
pmcid: 4473544
doi: 10.1128/JVI.00773-15
Colgrave, M. L. et al. Site occupancy and glycan compositional analysis of two soluble recombinant forms of the attachment glycoprotein of Hendra virus. Glycobiology 22, 572–584 (2012).
pubmed: 22171062
doi: 10.1093/glycob/cwr180
Colf, L. A., Juo, Z. S. & Garcia, K. C. Structure of the measles virus hemagglutinin. Nat. Struct. Mol. Biol. 14, 1227–1228 (2007).
pubmed: 18026116
doi: 10.1038/nsmb1342
Liu, Q. et al. Unraveling a three-step spatiotemporal mechanism of triggering of receptor-induced Nipah virus fusion and cell entry. PLoS Pathog. 9, e1003770 (2013).
pubmed: 24278018
pmcid: 3837712
doi: 10.1371/journal.ppat.1003770
Liu, Q. et al. Nipah virus attachment glycoprotein stalk C-terminal region links receptor binding to fusion triggering. J. Virol. 89, 1838–1850 (2015).
pubmed: 25428863
doi: 10.1128/JVI.02277-14
Stone, J. A., Vemulapati, B. M., Bradel-Tretheway, B. & Aguilar, H. C. Multiple Strategies Reveal a Bidentate Interaction between the Nipah Virus Attachment and Fusion Glycoproteins. J. Virol. 90, 10762–10773 (2016).
pubmed: 27654290
pmcid: 5110167
doi: 10.1128/JVI.01469-16
Ortega, V. et al. Novel Roles of the Nipah Virus Attachment Glycoprotein and Its Mobility in Early and Late Membrane Fusion Steps. mBio 13, e0322221 (2022).
pubmed: 35506666
doi: 10.1128/mbio.03222-21
Marcink, T. C. et al. Subnanometer structure of an enveloped virus fusion complex on viral surface reveals new entry mechanisms. Sci. Adv. 9, eade2727 (2023).
pubmed: 36763666
pmcid: 9917000
doi: 10.1126/sciadv.ade2727
Porotto, M., Murrell, M., Greengard, O. & Moscona, A. Triggering of human parainfluenza virus 3 fusion protein (F) by the hemagglutinin-neuraminidase (HN) protein: an HN mutation diminishes the rate of F activation and fusion. J. Virol. 77, 3647–3654 (2003).
pubmed: 12610140
pmcid: 149538
doi: 10.1128/JVI.77.6.3647-3654.2003
Deng, R., Wang, Z., Mirza, A. M. & Iorio, R. M. Localization of a domain on the paramyxovirus attachment protein required for the promotion of cellular fusion by its homologous fusion protein spike. Virology 209, 457–469 (1995).
pubmed: 7778280
doi: 10.1006/viro.1995.1278
Tanabayashi, K. & Compans, R. W. Functional interaction of paramyxovirus glycoproteins: identification of a domain in Sendai virus HN which promotes cell fusion. J. Virol. 70, 6112–6118 (1996).
pubmed: 8709235
pmcid: 190633
doi: 10.1128/jvi.70.9.6112-6118.1996
Brindley, M. A. et al. A stabilized headless measles virus attachment protein stalk efficiently triggers membrane fusion. J. Virol. 87, 11693–11703 (2013).
pubmed: 23966411
pmcid: 3807326
doi: 10.1128/JVI.01945-13
Amaya, M. & Broder, C. C. Vaccines to Emerging Viruses: Nipah and Hendra. Annu. Rev. Virol. 7, 447–473 (2020).
pubmed: 32991264
pmcid: 8782152
doi: 10.1146/annurev-virology-021920-113833
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
doi: 10.1038/nmeth.4193
Grant, T. & Grigorieff, N. Measuring the optimal exposure for single particle cryo-EM using a 2.6 A reconstruction of rotavirus VP6. Elife 4, e06980 (2015).
pubmed: 26023829
pmcid: 4471936
doi: 10.7554/eLife.06980
Zhang, K. Gctf: Real-time CTF determination and correction. J. Struct. Biol. 193, 1–12 (2016).
pubmed: 26592709
pmcid: 4711343
doi: 10.1016/j.jsb.2015.11.003
Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. Elife 7, https://doi.org/10.7554/eLife.42166 (2018).
Kimanius, D., Forsberg, B. O., Scheres, S. H. & Lindahl, E. Accelerated cryo-EM structure determination with parallelisation using GPUs in RELION-2. eLife 5, https://doi.org/10.7554/eLife.18722 (2016).
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
doi: 10.1016/j.jsb.2012.09.006
Scheres, S. H. A Bayesian view on cryo-EM structure determination. J. Mol. Biol. 415, 406–418 (2012).
pubmed: 22100448
pmcid: 3314964
doi: 10.1016/j.jmb.2011.11.010
Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).
pubmed: 28165473
doi: 10.1038/nmeth.4169
Rosenthal, P. B. & Henderson, R. Optimal determination of particle orientation, absolute hand, and contrast loss in single-particle electron cryomicroscopy. J. Mol. Biol. 333, 721–745 (2003).
pubmed: 14568533
doi: 10.1016/j.jmb.2003.07.013
Chen, S. et al. High-resolution noise substitution to measure overfitting and validate resolution in 3D structure determination by single particle electron cryomicroscopy. Ultramicroscopy 135, 24–35 (2013).
pubmed: 23872039
pmcid: 3834153
doi: 10.1016/j.ultramic.2013.06.004
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).
pubmed: 34265844
pmcid: 8371605
doi: 10.1038/s41586-021-03819-2
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. Sect. D Biol. Crystallogr. 66, 486–501 (2010).
doi: 10.1107/S0907444910007493
Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. Sect. D Biol. Crystallogr. 66, 213–221 (2010).
doi: 10.1107/S0907444909052925