Understanding Enterovirus 71 Neuropathogenesis and Its Impact on Other Neurotropic Enteroviruses

Overview

Journal Brain Pathol

Date 2015 Aug 16

PMID 26276025

Citations 41

Authors

Kien Chai Ong

Kum Thong Wong

Affiliations

Soon will be listed here.

Abstract

Enterovirus A71 (EV-A71) belongs to the species group A in the Enterovirus genus within the Picornaviridae family. EV-A71 usually causes self-limiting hand, foot and mouth disease or herpangina but rarely causes severe neurological complications such as acute flaccid paralysis and encephalomyelitis. The pathology and neuropathogenesis of these neurological syndromes is beginning to be understood. EV-A71 neurotropism for motor neurons in the spinal cord and brainstem, and other neurons, is mainly responsible for central nervous system damage. This review on the general aspects, recent developments and advances of EV-A71 infection will focus on neuropathogenesis and its implications on other neurotropic enteroviruses, such as poliovirus and the newly emergent Enterovirus D68. With the imminent eradication of poliovirus, EV-A71 is likely to replace it as an important neurotropic enterovirus of worldwide importance.

Citing Articles

Pathogenesis of enterovirus infection in central nervous system.

Wang C, Li J, Liu Y, Sun Q, Liu Z Biosaf Health. 2025; 5(4):233-239.

PMID: 40078226 PMC: 11894963. DOI: 10.1016/j.bsheal.2023.06.001.

The neurological damage caused by enterovirus 71 infection is associated with hsa_circ_0069335/miR-29b/PMP22 pathway.

Liu G, Zhu D, Feng K, Peng H, Yang S, Huang L J Virol. 2024; 99(1):e0084424.

PMID: 39636111 PMC: 11784151. DOI: 10.1128/jvi.00844-24.

Tanomastat exerts multi-targeted inhibitory effects on viral capsid dissociation and RNA replication in human enteroviruses.

Lim T, Jaladanki C, Wong Y, Yogarajah T, Fan H, Chu J EBioMedicine. 2024; 107:105277.

PMID: 39226680 PMC: 11419895. DOI: 10.1016/j.ebiom.2024.105277.

Correlations of PSGL-1 VNTR polymorphism with the susceptibility to severe HFMD associated with EV-71 and the immune status after infection.

Wang X, Qian J, Mi Y, Li Y, Cao Y, Qiao K Virol J. 2024; 21(1):187.

PMID: 39148126 PMC: 11328417. DOI: 10.1186/s12985-024-02461-4.

Changing Epidemiology of Hand, Foot, and Mouth Disease Causative Agents and Contributing Factors.

Kalam N, Balasubramaniam V Am J Trop Med Hyg. 2024; 111(4):740-755.

PMID: 39106854 PMC: 11448535. DOI: 10.4269/ajtmh.23-0852.

References

Wang S, Lei H, Huang K, Wu J, Wang J, Yu C . Pathogenesis of enterovirus 71 brainstem encephalitis in pediatric patients: roles of cytokines and cellular immune activation in patients with pulmonary edema. J Infect Dis. 2003; 188(4):564-70. DOI: 10.1086/376998. View

Lin Y, Wang S, Tung Y, Chen S . Enterovirus 71 infection of human dendritic cells. Exp Biol Med (Maywood). 2009; 234(10):1166-73. DOI: 10.3181/0903-RM-116. View

Mao Q, Wang Y, Gao R, Shao J, Yao X, Lang S . A neonatal mouse model of coxsackievirus A16 for vaccine evaluation. J Virol. 2012; 86(22):11967-76. PMC: 3486452. DOI: 10.1128/JVI.00902-12. View

Maloney J, Mirsky D, Messacar K, Dominguez S, Schreiner T, Stence N . MRI findings in children with acute flaccid paralysis and cranial nerve dysfunction occurring during the 2014 enterovirus D68 outbreak. AJNR Am J Neuroradiol. 2014; 36(2):245-50. PMC: 7965662. DOI: 10.3174/ajnr.A4188. 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

Hsueh C, Jung S, Shih S, Kuo T, Shieh W, Zaki S . Acute encephalomyelitis during an outbreak of enterovirus type 71 infection in Taiwan: report of an autopsy case with pathologic, immunofluorescence, and molecular studies. Mod Pathol. 2000; 13(11):1200-5. DOI: 10.1038/modpathol.3880222. View

Goto K, Sanefuji M, Kusuhara K, Nishimura Y, Shimizu H, Kira R . Rhombencephalitis and coxsackievirus A16. Emerg Infect Dis. 2009; 15(10):1689-91. PMC: 2866411. DOI: 10.3201/eid1510.090594. View

SCHMIDT N, LENNETTE E, Ho H . An apparently new enterovirus isolated from patients with disease of the central nervous system. J Infect Dis. 1974; 129(3):304-9. DOI: 10.1093/infdis/129.3.304. View

Ma E, Fung C, Yip S, Wong C, Chuang S, Tsang T . Estimation of the basic reproduction number of enterovirus 71 and coxsackievirus A16 in hand, foot, and mouth disease outbreaks. Pediatr Infect Dis J. 2011; 30(8):675-9. DOI: 10.1097/INF.0b013e3182116e95. View

10.

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

11.

Chen F, Liu T, Li J, Xing Z, Huang S, Wen G . MRI characteristics and follow-up findings in patients with neurological complications of enterovirus 71-related hand, foot, and mouth disease. Int J Clin Exp Med. 2014; 7(9):2696-704. PMC: 4211777. View

12.

Ooi M, Solomon T, Podin Y, Mohan A, Akin W, Yusuf M . Evaluation of different clinical sample types in diagnosis of human enterovirus 71-associated hand-foot-and-mouth disease. J Clin Microbiol. 2007; 45(6):1858-66. PMC: 1933032. DOI: 10.1128/JCM.01394-06. View

13.

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

14.

Wang J, Yao C, Yeh C, Huang C, Wang S, Liu C . Critical management in patients with severe enterovirus 71 infection. Pediatr Int. 2006; 48(3):250-6. DOI: 10.1111/j.1442-200X.2006.02198.x. View

15.

Lui Y, Tan E . Droplet digital PCR as a useful tool for the quantitative detection of Enterovirus 71. J Virol Methods. 2014; 207:200-3. DOI: 10.1016/j.jviromet.2014.07.014. View

16.

Plevka P, Perera R, Cardosa J, Kuhn R, Rossmann M . Crystal structure of human enterovirus 71. Science. 2012; 336(6086):1274. PMC: 3448362. DOI: 10.1126/science.1218713. View

17.

LUM L, Wong K, Lam S, Chua K, Goh A, Lim W . Fatal enterovirus 71 encephalomyelitis. J Pediatr. 1998; 133(6):795-8. DOI: 10.1016/s0022-3476(98)70155-6. View

18.

Ohka S, Nihei C, Yamazaki M, Nomoto A . Poliovirus trafficking toward central nervous system via human poliovirus receptor-dependent and -independent pathway. Front Microbiol. 2012; 3:147. PMC: 3328850. DOI: 10.3389/fmicb.2012.00147. View

19.

Wylie K, Wylie T, Orvedahl A, Buller R, Herter B, Magrini V . Genome sequence of enterovirus D68 from St. Louis, Missouri, USA. Emerg Infect Dis. 2014; 21(1):184-6. PMC: 4285240. DOI: 10.3201/eid2101.141605. View

20.

Koike S, Taya C, Kurata T, Abe S, Ise I, Yonekawa H . Transgenic mice susceptible to poliovirus. Proc Natl Acad Sci U S A. 1991; 88(3):951-5. PMC: 50932. DOI: 10.1073/pnas.88.3.951. View