Adaptation and Virulence of Enterovirus-A71

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2021 Aug 28

PMID 34452525

Citations 7

Authors

Kyousuke Kobayashi

Satoshi Koike

Affiliations

Soon will be listed here.

Abstract

Outbreaks of hand, foot, and mouth disease caused by enterovirus-A71 (EV-A71) can result in many deaths, due to central nervous system complications. Outbreaks with many fatalities have occurred sporadically in the Asia-Pacific region and have become a serious public health concern. It is hypothesized that virulent mutations in the EV-A71 genome cause these occasional outbreaks. Analysis of EV-A71 neurovirulence determinants is important, but there are no virulence determinants that are widely accepted among researchers. This is because most studies have been done in artificially infected mouse models and because EV-A71 mutates very quickly to adapt to the artificial host environment. Although EV-A71 uses multiple receptors for infection, it is clear that adaptation-related mutations alter the binding specificity of the receptors and allow the virus to adopt the best entry route for each environment. Such mutations have confused interpretations of virulence in animal models. This article will discuss how environment-adapted mutations in EV-A71 occur, how they affect virulence, and how such mutations can be avoided. We also discuss future perspectives for EV-A71 virulence research.

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References

Chang C, Liao C, Liou A, Chou Y, Yu Y, Lin C . Novel Naturally Occurring Mutations of Enterovirus 71 Associated With Disease Severity. Front Microbiol. 2021; 11:610568. PMC: 7838335. DOI: 10.3389/fmicb.2020.610568. View

Fu X, Wan Z, Li Y, Hu Y, Jin X, Zhang C . National Epidemiology and Evolutionary History of Four Hand, Foot and Mouth Disease-Related Enteroviruses in China from 2008 to 2016. Virol Sin. 2019; 35(1):21-33. PMC: 7035399. DOI: 10.1007/s12250-019-00169-2. View

Fujii K, Nagata N, Sato Y, Ong K, Wong K, Yamayoshi S . Transgenic mouse model for the study of enterovirus 71 neuropathogenesis. Proc Natl Acad Sci U S A. 2013; 110(36):14753-8. PMC: 3767555. DOI: 10.1073/pnas.1217563110. View

Nishimura Y, Lee H, Hafenstein S, Kataoka C, Wakita T, Bergelson J . Enterovirus 71 binding to PSGL-1 on leukocytes: VP1-145 acts as a molecular switch to control receptor interaction. PLoS Pathog. 2013; 9(7):e1003511. PMC: 3723564. DOI: 10.1371/journal.ppat.1003511. View

Tee H, Tan C, Yogarajah T, Lee M, Chai H, Hanapi N . Electrostatic interactions at the five-fold axis alter heparin-binding phenotype and drive enterovirus A71 virulence in mice. PLoS Pathog. 2019; 15(11):e1007863. PMC: 6881073. DOI: 10.1371/journal.ppat.1007863. View

Victorio C, Xu Y, Ng Q, Meng T, Chow V, Chua K . Cooperative effect of the VP1 amino acids 98E, 145A and 169F in the productive infection of mouse cell lines by enterovirus 71 (BS strain). Emerg Microbes Infect. 2016; 5:e60. PMC: 4932649. DOI: 10.1038/emi.2016.56. View

Nagata N, Shimizu H, Ami Y, Tano Y, Harashima A, Suzaki Y . Pyramidal and extrapyramidal involvement in experimental infection of cynomolgus monkeys with enterovirus 71. J Med Virol. 2002; 67(2):207-16. DOI: 10.1002/jmv.2209. View

Pfeiffer J, Kirkegaard K . Increased fidelity reduces poliovirus fitness and virulence under selective pressure in mice. PLoS Pathog. 2005; 1(2):e11. PMC: 1250929. DOI: 10.1371/journal.ppat.0010011. View

Tan C, Sam I, Lee V, Wong H, Chan Y . VP1 residues around the five-fold axis of enterovirus A71 mediate heparan sulfate interaction. Virology. 2016; 501:79-87. DOI: 10.1016/j.virol.2016.11.009. View

10.

Zhu J, Chen N, Zhou S, Zheng K, Sun L, Zhang Y . Severity of enterovirus A71 infection in a human SCARB2 knock-in mouse model is dependent on infectious strain and route. Emerg Microbes Infect. 2018; 7(1):205. PMC: 6281673. DOI: 10.1038/s41426-018-0201-3. View

11.

Lin Y, Yu S, Shao H, Lin H, Liu C, Hsiao K . Human SCARB2 transgenic mice as an infectious animal model for enterovirus 71. PLoS One. 2013; 8(2):e57591. PMC: 3581494. DOI: 10.1371/journal.pone.0057591. View

12.

Kataoka C, Suzuki T, Kotani O, Iwata-Yoshikawa N, Nagata N, Ami Y . The Role of VP1 Amino Acid Residue 145 of Enterovirus 71 in Viral Fitness and Pathogenesis in a Cynomolgus Monkey Model. PLoS Pathog. 2015; 11(7):e1005033. PMC: 4504482. DOI: 10.1371/journal.ppat.1005033. View

13.

Zhou D, Zhao Y, Kotecha A, Fry E, Kelly J, Wang X . Unexpected mode of engagement between enterovirus 71 and its receptor SCARB2. Nat Microbiol. 2018; 4(3):414-419. DOI: 10.1038/s41564-018-0319-z. View

14.

Yang S, Chou Y, Wu C, Ho M . Annexin II binds to capsid protein VP1 of enterovirus 71 and enhances viral infectivity. J Virol. 2011; 85(22):11809-20. PMC: 3209289. DOI: 10.1128/JVI.00297-11. View

15.

Li R, Zou Q, Chen L, Zhang H, Wang Y . Molecular analysis of virulent determinants of enterovirus 71. PLoS One. 2011; 6(10):e26237. PMC: 3198388. DOI: 10.1371/journal.pone.0026237. View

16.

He Q, Ren S, Xia Z, Cheng Z, Peng N, Zhu Y . Fibronectin Facilitates Enterovirus 71 Infection by Mediating Viral Entry. J Virol. 2018; 92(9). PMC: 5899198. DOI: 10.1128/JVI.02251-17. View

17.

Xu Y, Ma S, Zhu L, Huang Z, Chen L, Xu Y . Clinically isolated enterovirus A71 subgenogroup C4 strain with lethal pathogenicity in 14-day-old mice and the application as an EV-A71 mouse infection model. Antiviral Res. 2016; 137:67-75. DOI: 10.1016/j.antiviral.2016.11.008. View

18.

Victorio C, Xu Y, Ng Q, Chow V, Chua K . Phenotypic and genotypic characteristics of novel mouse cell line (NIH/3T3)-adapted human enterovirus 71 strains (EV71:TLLm and EV71:TLLmv). PLoS One. 2014; 9(3):e92719. PMC: 3966832. DOI: 10.1371/journal.pone.0092719. View

19.

Ke X, Zhang Y, Liu Y, Miao Y, Zheng C, Luo D . A Single Mutation in the VP1 Gene of Enterovirus 71 Enhances Viral Binding to Heparan Sulfate and Impairs Viral Pathogenicity in Mice. Viruses. 2020; 12(8). PMC: 7472116. DOI: 10.3390/v12080883. View

20.

Shih S, Ho M, Lin K, Wu S, Chen Y, Wu C . Genetic analysis of enterovirus 71 isolated from fatal and non-fatal cases of hand, foot and mouth disease during an epidemic in Taiwan, 1998. Virus Res. 2000; 68(2):127-36. DOI: 10.1016/s0168-1702(00)00162-3. View