Not Your Usual TRNA Synthetase: HWARS Serves As an Enterovirus Entry Factor

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2018 Oct 16

PMID 30320601

Citations 3

Authors

Stanley Perlman

Tom Gallagher

Affiliations

Soon will be listed here.

Abstract

Enteroviruses, including subtype EV-A71, infect the brain, liver, heart, and other organs, causing a myriad of human diseases. This spectrum of disease is thought to be due, in part, to differential binding to host cells, and additional knowledge of enterovirus cell entry is essential for therapeutic development. In this issue of the JCI, Yeung et al. provide evidence of a novel EV-A71 entry factor, a host-produced tryptophan tRNA synthetase (hWARS), that facilitates entry of multiple subtypes of enteroviruses. hWARS is a cytoplasmic enzyme that is essential for translation but also upregulated and secreted during inflammatory processes. The results of this study support the notion of secreted hWARS as an unconventional virus entry factor that raises interesting questions about mechanisms by which inflammation and a tRNA synthetase facilitate viral pathogenesis.

Citing Articles

Mechanistic perspectives on anti-aminoacyl-tRNA synthetase syndrome.

Kanaji S, Chen W, Morodomi Y, Shapiro R, Kanaji T, Yang X Trends Biochem Sci. 2022; 48(3):288-302.

PMID: 36280495 PMC: 9974581. DOI: 10.1016/j.tibs.2022.09.011.

Tryptophan Depletion Modulates Tryptophanyl-tRNA Synthetase-Mediated High-Affinity Tryptophan Uptake into Human Cells.

Yokosawa T, Sato A, Wakasugi K Genes (Basel). 2020; 11(12).

PMID: 33261077 PMC: 7760169. DOI: 10.3390/genes11121423.

Recent advances on the role of host factors during non-poliovirus enteroviral infections.

Owino C, Chu J J Biomed Sci. 2019; 26(1):47.

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References

Tzima E, Reader J, Irani-Tehrani M, Ewalt K, Schwartz M, Schimmel P . VE-cadherin links tRNA synthetase cytokine to anti-angiogenic function. J Biol Chem. 2004; 280(4):2405-8. DOI: 10.1074/jbc.C400431200. View

Bhutia Y, Babu E, Ganapathy V . Interferon-γ induces a tryptophan-selective amino acid transporter in human colonic epithelial cells and mouse dendritic cells. Biochim Biophys Acta. 2014; 1848(2):453-62. DOI: 10.1016/j.bbamem.2014.10.021. View

Stockinger B, Di Meglio P, Gialitakis M, Duarte J . The aryl hydrocarbon receptor: multitasking in the immune system. Annu Rev Immunol. 2014; 32:403-32. DOI: 10.1146/annurev-immunol-032713-120245. View

Miyanokoshi M, Yokosawa T, Wakasugi K . Tryptophanyl-tRNA synthetase mediates high-affinity tryptophan uptake into human cells. J Biol Chem. 2018; 293(22):8428-8438. PMC: 5986205. DOI: 10.1074/jbc.RA117.001247. View

Xing J, Liu D, Shen S, Su Z, Zhang L, Duan Y . Pathologic Studies of Fatal Encephalomyelitis in Children Caused by Enterovirus 71. Am J Clin Pathol. 2016; 146(1):95-106. DOI: 10.1093/ajcp/aqw089. View

Cheng Y . Single-particle cryo-EM-How did it get here and where will it go. Science. 2018; 361(6405):876-880. PMC: 6460916. DOI: 10.1126/science.aat4346. View

Yamayoshi S, Yamashita Y, Li J, Hanagata N, Minowa T, Takemura T . Scavenger receptor B2 is a cellular receptor for enterovirus 71. Nat Med. 2009; 15(7):798-801. DOI: 10.1038/nm.1992. View

Monteleone M, Stow J, Schroder K . Mechanisms of unconventional secretion of IL-1 family cytokines. Cytokine. 2015; 74(2):213-8. DOI: 10.1016/j.cyto.2015.03.022. View

Nishimura Y, Shimojima M, Tano Y, Miyamura T, Wakita T, Shimizu H . Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71. Nat Med. 2009; 15(7):794-7. DOI: 10.1038/nm.1961. View

10.

Yeung M, Jia L, Yip C, Chan J, Teng J, Chan K . Human tryptophanyl-tRNA synthetase is an IFN-γ-inducible entry factor for Enterovirus. J Clin Invest. 2018; 128(11):5163-5177. PMC: 6205371. DOI: 10.1172/JCI99411. View

11.

Mao Q, Wang Y, Bian L, Xu M, Liang Z . EV-A71 vaccine licensure: a first step for multivalent enterovirus vaccine to control HFMD and other severe diseases. Emerg Microbes Infect. 2016; 5(7):e75. PMC: 5141264. DOI: 10.1038/emi.2016.73. View

12.

Baggen J, Thibaut H, Strating J, van Kuppeveld F . The life cycle of non-polio enteroviruses and how to target it. Nat Rev Microbiol. 2018; 16(6):368-381. DOI: 10.1038/s41579-018-0005-4. View

13.

Blake I, Pons-Salort M, Molodecky N, Diop O, Chenoweth P, Bandyopadhyay A . Type 2 Poliovirus Detection after Global Withdrawal of Trivalent Oral Vaccine. N Engl J Med. 2018; 379(9):834-845. PMC: 5985919. DOI: 10.1056/NEJMoa1716677. View

14.

Zhao X, Guo F, Liu F, Cuconati A, Chang J, Block T . Interferon induction of IFITM proteins promotes infection by human coronavirus OC43. Proc Natl Acad Sci U S A. 2014; 111(18):6756-61. PMC: 4020042. DOI: 10.1073/pnas.1320856111. View

15.

Bitnun A, Yeh E . Acute Flaccid Paralysis and Enteroviral Infections. Curr Infect Dis Rep. 2018; 20(9):34. DOI: 10.1007/s11908-018-0641-x. View

16.

Ahn Y, Park S, Choi J, Park B, Rhee K, Kang E . Secreted tryptophanyl-tRNA synthetase as a primary defence system against infection. Nat Microbiol. 2016; 2:16191. DOI: 10.1038/nmicrobiol.2016.191. View

17.

Katzelnick L, Gresh L, Halloran M, Mercado J, Kuan G, Gordon A . Antibody-dependent enhancement of severe dengue disease in humans. Science. 2017; 358(6365):929-932. PMC: 5858873. DOI: 10.1126/science.aan6836. View

18.

Wakasugi K, Slike B, Hood J, Otani A, Ewalt K, Friedlander M . A human aminoacyl-tRNA synthetase as a regulator of angiogenesis. Proc Natl Acad Sci U S A. 2002; 99(1):173-7. PMC: 117534. DOI: 10.1073/pnas.012602099. View

19.

Morizono K, Xie Y, Olafsen T, Lee B, Dasgupta A, Wu A . The soluble serum protein Gas6 bridges virion envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry. Cell Host Microbe. 2011; 9(4):286-98. PMC: 3095825. DOI: 10.1016/j.chom.2011.03.012. View

20.

Yamayoshi S, Iizuka S, Yamashita T, Minagawa H, Mizuta K, Okamoto M . Human SCARB2-dependent infection by coxsackievirus A7, A14, and A16 and enterovirus 71. J Virol. 2012; 86(10):5686-96. PMC: 3347270. DOI: 10.1128/JVI.00020-12. View