A Key Region of Molecular Specificity Orchestrates Unique Ephrin-B1 Utilization by Cedar Virus

Overview

Journal Life Sci Alliance

Specialties Biochemistry
Biology
Cell Biology
Molecular Biology

Date 2019 Dec 22

PMID 31862858

Citations 21

Authors

Rhys Pryce

Kristopher Azarm

Ilona Rissanen

Karl Harlos

Thomas A Bowden

Benhur Lee

Affiliations

Soon will be listed here.

Abstract

The emergent zoonotic henipaviruses, Hendra, and Nipah are responsible for frequent and fatal disease outbreaks in domestic animals and humans. Specificity of henipavirus attachment glycoproteins (G) for highly species-conserved ephrin ligands underpins their broad host range and is associated with systemic and neurological disease pathologies. Here, we demonstrate that Cedar virus (CedV)-a related henipavirus that is ostensibly nonpathogenic-possesses an idiosyncratic entry receptor repertoire that includes the common henipaviral receptor, ephrin-B2, but, distinct from pathogenic henipaviruses, does not include ephrin-B3. Uniquely among known henipaviruses, CedV can use ephrin-B1 for cellular entry. Structural analyses of CedV-G reveal a key region of molecular specificity that directs ephrin-B1 utilization, while preserving a universal mode of ephrin-B2 recognition. The structural and functional insights presented uncover diversity within the known henipavirus receptor repertoire and suggest that only modest structural changes may be required to modulate receptor specificities within this group of lethal human pathogens.

Citing Articles

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References

Kubota M, Takeuchi K, Watanabe S, Ohno S, Matsuoka R, Kohda D . Trisaccharide containing α2,3-linked sialic acid is a receptor for mumps virus. Proc Natl Acad Sci U S A. 2016; 113(41):11579-11584. PMC: 5068328. DOI: 10.1073/pnas.1608383113. View

Mbuu C, Mbacham W, Gontao P, Kamdem S, Njan Nloga A, Groschup M . Henipaviruses at the Interface Between Bats, Livestock and Human Population in Africa. Vector Borne Zoonotic Dis. 2019; 19(7):455-465. DOI: 10.1089/vbz.2018.2365. View

Lo M, Peeples M, Bellini W, Nichol S, Rota P, Spiropoulou C . Distinct and overlapping roles of Nipah virus P gene products in modulating the human endothelial cell antiviral response. PLoS One. 2012; 7(10):e47790. PMC: 3477106. DOI: 10.1371/journal.pone.0047790. View

Lim C, Sitoh Y, Hui F, Lee K, Ang B, Lim E . Nipah viral encephalitis or Japanese encephalitis? MR findings in a new zoonotic disease. AJNR Am J Neuroradiol. 2000; 21(3):455-61. PMC: 8174990. View

Pryce R, Ng W, Zeltina A, Watanabe Y, El Omari K, Wagner A . Structure-Based Classification Defines the Discrete Conformational Classes Adopted by the Arenaviral GP1. J Virol. 2018; 93(1). PMC: 6288339. DOI: 10.1128/JVI.01048-18. View

Walter T, Diprose J, Mayo C, Siebold C, Pickford M, Carter L . A procedure for setting up high-throughput nanolitre crystallization experiments. Crystallization workflow for initial screening, automated storage, imaging and optimization. Acta Crystallogr D Biol Crystallogr. 2005; 61(Pt 6):651-7. PMC: 7159505. DOI: 10.1107/S0907444905007808. View

Chua K, Bellini W, Rota P, Harcourt B, Tamin A, Lam S . Nipah virus: a recently emergent deadly paramyxovirus. Science. 2000; 288(5470):1432-5. DOI: 10.1126/science.288.5470.1432. View

Ang B, Lim T, Wang L . Nipah Virus Infection. J Clin Microbiol. 2018; 56(6). PMC: 5971524. DOI: 10.1128/JCM.01875-17. View

Nikolay B, Salje H, Hossain M, Khan A, Sazzad H, Rahman M . Transmission of Nipah Virus - 14 Years of Investigations in Bangladesh. N Engl J Med. 2019; 380(19):1804-1814. PMC: 6547369. DOI: 10.1056/NEJMoa1805376. View

10.

Corpet F . Multiple sequence alignment with hierarchical clustering. Nucleic Acids Res. 1988; 16(22):10881-90. PMC: 338945. DOI: 10.1093/nar/16.22.10881. View

11.

Lee B, Ataman Z . Modes of paramyxovirus fusion: a Henipavirus perspective. Trends Microbiol. 2011; 19(8):389-99. PMC: 3264399. DOI: 10.1016/j.tim.2011.03.005. View

12.

Chang V, Crispin M, Aricescu A, Harvey D, Nettleship J, Fennelly J . Glycoprotein structural genomics: solving the glycosylation problem. Structure. 2007; 15(3):267-73. PMC: 1885966. DOI: 10.1016/j.str.2007.01.011. View

13.

Li Y, Wang J, Hickey A, Zhang Y, Li Y, Wu Y . Antibodies to Nipah or Nipah-like viruses in bats, China. Emerg Infect Dis. 2008; 14(12):1974-6. PMC: 2634619. DOI: 10.3201/eid1412.080359. View

14.

Blits-Huizinga C, Nelersa C, Malhotra A, Liebl D . Ephrins and their receptors: binding versus biology. IUBMB Life. 2004; 56(5):257-65. DOI: 10.1080/15216540412331270076. View

15.

Halpin K, Hyatt A, Fogarty R, Middleton D, Bingham J, Epstein J . Pteropid bats are confirmed as the reservoir hosts of henipaviruses: a comprehensive experimental study of virus transmission. Am J Trop Med Hyg. 2011; 85(5):946-51. PMC: 3205647. DOI: 10.4269/ajtmh.2011.10-0567. View

16.

Aricescu A, Lu W, Jones E . A time- and cost-efficient system for high-level protein production in mammalian cells. Acta Crystallogr D Biol Crystallogr. 2006; 62(Pt 10):1243-50. DOI: 10.1107/S0907444906029799. View

17.

Yokoyama N, Romero M, Cowan C, Galvan P, Helmbacher F, Charnay P . Forward signaling mediated by ephrin-B3 prevents contralateral corticospinal axons from recrossing the spinal cord midline. Neuron. 2001; 29(1):85-97. DOI: 10.1016/s0896-6273(01)00182-9. View

18.

Agirre J, Iglesias-Fernandez J, Rovira C, Davies G, Wilson K, Cowtan K . Privateer: software for the conformational validation of carbohydrate structures. Nat Struct Mol Biol. 2015; 22(11):833-4. DOI: 10.1038/nsmb.3115. View

19.

Thibault P, Watkinson R, Moreira-Soto A, Drexler J, Lee B . Zoonotic Potential of Emerging Paramyxoviruses: Knowns and Unknowns. Adv Virus Res. 2017; 98:1-55. PMC: 5894875. DOI: 10.1016/bs.aivir.2016.12.001. View

20.

Bradel-Tretheway B, Liu Q, Stone J, McInally S, Aguilar H . Novel Functions of Hendra Virus G N-Glycans and Comparisons to Nipah Virus. J Virol. 2015; 89(14):7235-47. PMC: 4473544. DOI: 10.1128/JVI.00773-15. View