Recent advances in the understanding of enterovirus A71 infection: a focus on neuropathogenesis

References

• Nik Nadia N, Sam I C, Rampal S, Wan Nor Amalina W, NurAtifahG, Verasahib K, et al. Cyclical patterns of hand, foot and mouth disease caused by enterovirus A71 in Malaysia. PLoS Negl Trop Dis. 2016; 10(3).
   Web of Science ®Google Scholar
• Solomon T, Lewthwaite P, Perera D, Cardosa MJ, McMinn P, Ooi MH. Virology, epidemiology, pathogenesis, and control of enterovirus 71. Lancet Infect Dis. 2010;10(11):778–790.
   PubMed Web of Science ®Google Scholar
• Schmidt NJ, Lennette EH, Ho HH. An apparently new enterovirus isolated from patients with disease of the central nervous system. J Infect Dis. 1974;129(3):304–309.
   PubMed Web of Science ®Google Scholar
• Ooi MH, Wong SC, Lewthwaite P, Cardosa MJ, Solomon T. Clinical features, diagnosis, and management of enterovirus 71. Lancet Neurol. 2010;9(11):1097–1105.
   PubMed Web of Science ®Google Scholar
• Gao LD, Hu SX, Zhang H, Luo KW, Liu YZ, Xu QH, et al. . Correlation analysis of EV71 detection and case severity in hand, foot, and mouth disease in the Hunan Province of China. PLoS One. 2014;9:6.
   Web of Science ®Google Scholar
• Sabanathan S, Tan LV, Thwaites L, Wills B, Qui PT. Rogier van Doorn H. Enterovirus 71 related severe hand, foot and mouth disease outbreaks in South-East Asia: current situation and ongoing challenges. J Epidemiol Community Health. 2014;68(6):500–502.
   PubMed Web of Science ®Google Scholar
• Xing W, Liao Q, Viboud C, Zhang J, Sun J, Wu JT, et al. . Hand, foot, and mouth disease in China, 2008-12: an epidemiological study. Lancet Infect Dis. 2014;14(4):308–318.
   PubMed Web of Science ®Google Scholar
• Zhang J, Sun J, Chang Z, Zhang W, Wang Z, Feng Z. Characteriza-tion of hand, foot, and mouth disease in China between 2008 and 2009. Biomed Environ Sci. 2011;24(3):214–221.
   PubMed Web of Science ®Google Scholar
• Mc Minn PC. An overview of the evolution of enterovirus 71 and its clinical and public health significance. FEMS Microbiol Rev. 2002;26(1):91–107.
   PubMed Web of Science ®Google Scholar
• Zhu F, Xu W, Xia J, Liang Z, Liu Y, Zhang X, et al. . Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China. N Engl J Med. 2014;370(9):818–828.
   PubMed Web of Science ®Google Scholar
• Plevka P, Perera R, Yap ML, Cardosa J, Kuhn RJ, Rossmann MG. Structure of human enterovirus 71 in complex with a capsid-binding inhibitor. Proc Natl Acad Sci USA. 2013;110(14):5463–5467.
   PubMed Web of Science ®Google Scholar
• Baggen J, Thibaut HJ, Strating J, van Kuppeveld FJM. The life cycle of non-polio enteroviruses and how to target it. Nat Rev Microbiol. 2018;16(6):368–381.
   PubMed Web of Science ®Google Scholar
• Yi L, Lu J, Kung HF, He ML. The virology and developments toward control of human enterovirus 71. Crit Rev Microbiol. 2011;37(4):313–327.
   PubMed Web of Science ®Google Scholar
• Hindiyeh M, Li QH, Basavappa R, Hogle JM, Chow M. Poliovirus mutants at histidine 195 of VP2 do not cleave VP0 into VP2 and VP4. J Virol. 1999;73(11):9072–9079.
   PubMed Web of Science ®Google Scholar
• Veesler D, Johnson JE. Virus maturation. Annu Rev Biophys. 2012;41:473–496.
   PubMed Web of Science ®Google Scholar
• Shih SR, Weng KF, Stollar V, Li ML. Viral protein synthesis is required for enterovirus 71 to induce apoptosis in human glioblastoma cells. J Neurovirol. 2008;14(1):53–61.
   PubMed Web of Science ®Google Scholar
• Sun D, Wen X, Wang M, Mao S, Cheng A, Yang X, et al. Apoptosis and autophagy in picornavirus infection. Front Microbiol. 2019;10:2032.
   PubMed Web of Science ®Google Scholar
• Too IHK, Yeo H, Sessions OM, Yan B, Libau EA, Howe JLC, et al. . Enterovirus 71 infection of motor neuron-like NSC-34 cells undergoes a non-lytic exit pathway. Sci Rep. 2016;6(1):36983.
   PubMedGoogle Scholar
• Lai JK, Sam IC, Chan YF. The Autophagic machinery in enterovirus infection. Viruses. 2016;8(2):32.
   Web of Science ®Google Scholar
• Chang LY, Hsia SH, Wu CT, Huang YC, Lin KL, Fang TY, et al. . Outcome of enterovirus 71 infections with or without stage-based management: 1998 to 2002. Pediatr Infect Dis J. 2004;23(4):327–332.
   PubMed Web of Science ®Google Scholar
• Ni XF, Li X, Xu C, Xiong Q, Xie BY, Wang LH, et al. . Risk factors for death from hand-foot-mouth disease: a meta-analysis. Epidemiol Infect. 2020;148:e44.
   PubMed Web of Science ®Google Scholar
• Chang LY, Huang LM, Gau SSF, Wu YY, Hsia SH, Fan TY, et al. . Neurodevelopment and cognition in children after enterovirus 71 infection. N Engl J Med. 2007;356(12):1226–1234.
   PubMed Web of Science ®Google Scholar
• Huang MC, Wang SM, Hsu YW, Lin HC, Chi CY, Liu CC. Long-term cognitive and motor deficits after enterovirus 71 brainstem encephalitis in children. Pediatrics. 2006;118(6):e1785–e8.
   PubMed Web of Science ®Google Scholar
• Huang CC, Liu CC, Chang YC, Chen CY, Wang ST, Yeh TF. Neurologic complications in children with enterovirus 71 infection. N Engl J Med. 1999;341(13):936–942.
   PubMed Web of Science ®Google Scholar
• Xing J, Liu D, Shen S, Su Z, Zhang L, Duan Y, et al. . Pathologic studies of fatal encephalomyelitis in children caused by enterovirus 71. Am J Clin Pathol. 2016;146(1):95–106.
   PubMed Web of Science ®Google Scholar
• Gao L, Lin P, Liu S, Lei B, Chen Q, Yu S, et al. Pathological examinations of an enterovirus 71 infection: an autopsy case. Int J Clin Exp Pathol. 2014;7(8):5236–5241.
   PubMed Web of Science ®Google Scholar
• Xing J, Wang K, Wei H, Wei D. Pathologic and molecular studies of enterovirus 71 infection in a fatal case from a recent epidemic in China: a case report. Medicine (Baltimore). 2018;97(48):e13447.
   PubMed Web of Science ®Google Scholar
• Hsueh C, Jung SM, Shih SR, Kuo TT, Shieh WJ, Zaki S, et al. . 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):1200–1205.
   PubMed Web of Science ®Google Scholar
• Yan JJ, Wang JR, Liu CC, Yang HB, Su IJ. An outbreak of enterovirus 71 infection in Taiwan 1998: a comprehensive pathological, virological, and molecular study on a case of fulminant encephalitis. J Clin Virol. 2000;17(1):13–22.
   PubMed Web of Science ®Google Scholar
• Shen WC, Chiu HH, Chow KC, Tsai CH. MR imaging findings of enteroviral encephaloymelitis: an outbreak in Taiwan. AJNR Am J Neuroradiol. 1999;20(10):1889–1895.
   PubMedGoogle Scholar
• Wong KT, Ng KY, Ong KC, Ng WF, Shankar SK, Mahadevan A, et al. . Enterovirus 71 encephalomyelitis and Japanese encephalitis can be distinguished by topographic distribution of inflammation and specific intraneuronal detection of viral antigen and RNA. Neuropathol Appl Neurobiol. 2012;38(5):443–453.
   PubMed Web of Science ®Google Scholar
• Ong KC, Wong KT. Understanding enterovirus 71 neuropathogenesis and its impact on other neurotropic enteroviruses. Brain Pathol. 2015;25(5):614–624.
   PubMed Web of Science ®Google Scholar
• Chang LY, Lin TY, Hsu KH, Huang YC, Lin KL, Hsueh C, et al. . Clinical features and risk factors of pulmonary oedema after enterovirus-71-related hand, foot, and mouth disease. Lancet. 1999;354(9191):1682–1686.
   PubMed Web of Science ®Google Scholar
• Lum LC, Wong KT, Lam SK, Chua KB, Goh AY, Lim WL, et al. . Fatal enterovirus 71 encephalomyelitis. J Pediatr. 1998;133(6):795–798.
   PubMed Web of Science ®Google Scholar
• Kao SJ, Yang FL, Hsu YH, Chen HI. Mechanism of fulminant pulmonary oedema caused by enterovirus 71. Clin Infect Dis. 2004;38(12):1784–1788.
   PubMed Web of Science ®Google Scholar
• Chang LY, Huang YC, Lin TY. Fulminant neurogenic pulmonary oedema with hand, foot, and mouth disease. Lancet. 1998;352(9125):367–368.
   PubMed Web of Science ®Google Scholar
• Lin TY, Hsia SH, Huang YC, Wu CT, Chang LY. Proinflammatory cytokine reactions in enterovirus 71 infections of the central nervous system. Clin Infect Dis. 2003;36(3):269–274.
   PubMed Web of Science ®Google Scholar
• Huang FL, Jan SL, Chen PY, Chi CS, Wang TM, Fu YC, et al. . Left ventricular dysfunction in children with fulminant enterovirus 71 infection: an evaluation of the clinical course. Clin Infect Dis. 2002;34(7):1020–1024.
   PubMed Web of Science ®Google Scholar
• Fu YC, Chi CS, Jan SL, Wang TM, Chen PY, Chang Y, et al. . Pulmonary oedema of enterovirus 71 encephalomyelitis is associated with left ventricular failure: implications for treatment. Pediatr Pulmonol. 2003;35(4):263–268.
   PubMed Web of Science ®Google Scholar
• Pallansch M, Roos R. Fields virology. In: Knipe D, Howley P, editors. Enteroviruses: polioviruses, coxsackieviruses, echoviruses and newer enteroviruses. 5th ed ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007. p. 655–705.
   Google Scholar
• Ooi MH, Solomon T, Podin Y, Mohan A, Akin W, Yusuf MA, et al. . Evaluation of different clinical sample types in diagnosis of human enterovirus 71-associated hand-foot-and-mouth disease. J Clin Microbiol. 2007;45(6):1858–1866.
   PubMed Web of Science ®Google Scholar
• Hussain KM, Leong KL, Ng MM, Chu JJ. The essential role of clathrin-mediated endocytosis in the infectious entry of human enterovirus 71. J Biol Chem. 2011;286(1):309–321.
   PubMed Web of Science ®Google Scholar
• Lin HY, Yang YT, Yu SL, Hsiao KN, Liu CC, Sia C, et al. . Caveolar endocytosis is required for human PSGL-1-mediated enterovirus-71 infection. J Virol. 2013;87(16):9064–9076.
   PubMed Web of Science ®Google Scholar
• Yamayoshi S, Yamashita Y, Li J, Hanagata N, Minowa T, Takemura T, et al. . Scavenger receptor B2 is a cellular receptor for enterovirus 71. Nat Med. 2009;15(7):798–801.
   PubMed Web of Science ®Google Scholar
• 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):794–797.
   PubMed Web of Science ®Google Scholar
• Tan CW, Poh CL, Sam IC, Chan YF. Enterovirus 71 uses cell surface heparan sulfate glycosaminoglycan as an attachment receptor. J Virol. 2013;87(1):611–620.
   PubMed Web of Science ®Google Scholar
• Su PY, Liu YT, Chang HY, Huang SW, Wang YF, Yu CK, et al. . Cell surface sialylation affects binding of enterovirus 71 to rhabdomyosarcoma and neuroblastoma cells. BMC Microbiol. 2012;12(1):162.
   PubMedGoogle Scholar
• Yang B, Solakyildirim K, Chang Y, Linhardt RJ. Hyphenated techniques for the analysis of heparin and heparan sulfate. Anal Bioanal Chem. 2011;399(2):541–557.
   PubMed Web of Science ®Google Scholar
• Du N, Cong H, Tian H, Zhang H, Zhang W, Song L, et al. . Cell surface vimentin is an attachment receptor for enterovirus 71. J Virol. 2014;88(10):5816–5833.
   PubMed Web of Science ®Google Scholar
• Su PY, Wang YF, Huang SW, Lo YC, Wang YH, Wu SR, et al. . Cell surface nucleolin facilitates enterovirus 71 binding and infection. J Virol. 2015;89(8):4527–4538.
   PubMed Web of Science ®Google Scholar
• Too IHK, Bonne I, Tan EL, Chu JJH, Alonso S. Prohibitin plays a critical role in enterovirus 71 neuropathogenesis. PLoS Pathog. 2018;14:1.
   Web of Science ®Google Scholar
• Yamayoshi S, Ohka S, Fujii K, Koike S. Functional comparison of SCARB2 and PSGL1 as receptors for enterovirus 71. J Virol. 2013;87(6):3335–3347.
   PubMed Web of Science ®Google Scholar
• Calvo D, Dopazo J, Vega MA. The CD36, CLA-1 (CD36L1), and LIMPII (CD36L2) gene family: cellular distribution, chromosomal location, and genetic evolution. Genomics. 1995;25(1):100–106.
   PubMed Web of Science ®Google Scholar
• Fujii K, Nagata N, Sato Y, Ong KC, Wong KT, Yamayoshi S, et al. . Transgenic mouse model for the study of enterovirus 71 neuropathogenesis. Proc Natl Acad Sci USA. 2013;110(36):14753–14758.
   PubMed Web of Science ®Google Scholar
• Lin YW, Yu SL, Shao HY, Lin HY, Liu CC, Hsiao KN, et al. Human SCARB2 transgenic mice as an infectious animal model for enterovirus 71. PLoS One. 2013;8:2.
   Web of Science ®Google Scholar
• Chen P, Song Z, Qi Y, Feng X, Xu N, Sun Y, et al. . Molecular determinants of enterovirus 71 viral entry: cleft around GLN-172 on VP1 protein interacts with variable region on scavenge receptor B2. J Biol Chem. 2012;287(9):6406–6420.
   PubMed Web of Science ®Google Scholar
• Zhou D, Zhao Y, Kotecha A, Fry EE, Kelly JT, Wang X, et al. . Unexpected mode of engagement between enterovirus 71 and its receptor SCARB2. Nat Microbiol. 2019;4(3):414–419.
   PubMed Web of Science ®Google Scholar
• Somers WS, Tang J, Shaw GD, Camphausen RT. Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound to SLe(X) and PSGL-1. Cell. 2000;103(3):467–479.
   PubMed Web of Science ®Google Scholar
• Laszik Z, Jansen PJ, Cummings RD, Tedder TF, McEver RP, Moore KL. P-selectin glycoprotein ligand-1 is broadly expressed in cells of myeloid, lymphoid, and dendritic lineage and in some nonhematopoietic cells. Blood. 1996;88(8):3010–3021.
   PubMed Web of Science ®Google Scholar
• Nishimura Y, Lee H, Hafenstein S, Kataoka C, Wakita T, Bergelson JM, et al. . Enterovirus 71 binding to PSGL-1 on leukocytes: VP1-145 acts as a molecular switch to control receptor interaction. PLoS Pathog. 2013;9:7.
   Web of Science ®Google Scholar
• Liu J, Dong W, Quan X, Ma C, Qin C, Zhang L. Transgenic expression of human P-selectin glycoprotein ligand-1 is not sufficient for enterovirus 71 infection in mice. Arch Virol. 2012;157(3):539–543.
   PubMed Web of Science ®Google Scholar
• Kjellen L, Oldberg A, Hook M. Cell-surface heparan sulfate. Mechanisms of proteoglycan-cell association. J Biol Chem. 1980;255(21):10407–10413.
   PubMed Web of Science ®Google Scholar
• Sarrazin S, Lamanna WC, Esko JD. Heparan sulfate proteoglycans. Cold Spring Harb Perspect Biol. 2011;3:7.
   PubMed Web of Science ®Google Scholar
• Zhu W, Li J, Liang G. How does cellular heparan sulfate function in viral pathogenicity?. Biomed Environ Sci. 2011;24(1):81–87.
   PubMed Web of Science ®Google Scholar
• Tan CW, Sam IC, Lee VS, Wong HV, Chan YF. VP1 residues around the five-fold axis of enterovirus A71 mediate heparan sulfate interaction. Virology. 2017;501:79–87.
   PubMed Web of Science ®Google Scholar
• Tee HK, Tan CW, Yogarajah T, Lee MHP, Chai HJ, Hanapi NA, et al. . Electrostatic interactions at the five-fold axis alter heparin-binding phenotype and drive enterovirus A71 virulence in mice. PLoS Pathog. 2019;15:11.
   Web of Science ®Google Scholar
• He Y, Ong KC, Gao Z, Zhao X, Anderson VM, McNutt MA, et al. , Tonsillar crypt epithelium is an important extra-central nervous system site for viral replication in EV71 encephalomyelitis. Am J Pathol. 184(3): 714–720. 2014.
   PubMed Web of Science ®Google Scholar
• Yin-Murphy M, Almond J. Medical Microbiology. In: editor, Baron S. Picornaviruses. 4th ed ed. Galveston (TX): University of Texas Medical Branch at Galveston; 1996.
   Google Scholar
• Zhao T, Zhang Z, Zhang Y, Feng M, Fan S, Wang L, et al. Dynamic interaction of enterovirus 71 and dendritic cells in infected neonatal rhesus macaques. Front Cell Infect Microbiol. 2017;7:171.
   PubMed Web of Science ®Google Scholar
• Sun L, Tijsma A, Mirabelli C, Baggen J, Wahedi M, Franco D, et al. . Intra-host emergence of an enterovirus A71 variant with enhanced PSGL1 usage and neurovirulence. Emerg Microbes Infect. 2019;8(1):1076–1085.
   PubMed Web of Science ®Google Scholar
• Victorio CB, Xu Y, Ng Q, Chua BH, Alonso S, Chow VT, et al. . A clinically authentic mouse model of enterovirus 71 (EV-A71)-induced neurogenic pulmonary oedema. Sci Rep. 2016;6:28876.
   PubMed Web of Science ®Google Scholar
• Jin Y, Zhang C, Wang H, Zhou G, Wang X, Zhang R, et al. Mast cells contribute to enterovirus 71 infection-induced pulmonary oedema in neonatal mice. Lab Invest. 2018;98(8):1039–1051.
   PubMed Web of Science ®Google Scholar
• Chang CS, Liao CC, Liou AT, Chang YS, Chang YT, Tzeng BH, et al. . Enterovirus 71 targets the cardiopulmonary system in a robust oral infection mouse model. Sci Rep. 2019;9(1):11108.
   PubMedGoogle Scholar
• Zhang Y, Cui W, Liu L, Wang J, Zhao H, Liao Y, et al. Pathogenesis study of enterovirus 71 infection in rhesus monkeys. Lab Invest. 2011;91(9):1337–1350.
   PubMed Web of Science ®Google Scholar
• Nagata N, Iwasaki T, Ami Y, Tano Y, Harashima A, Suzaki Y, et al. Differential localization of neurons susceptible to enterovirus 71 and poliovirus type 1 in the central nervous system of cynomolgus monkeys after intravenous inoculation. J Gen Virol. 2004;85(10):2981–2989.
   PubMedGoogle Scholar
• Ong KC, Badmanathan M, Devi S, Leong KL, Cardosa MJ, Wong KT. Pathologic characterization of a murine model of human enterovirus 71 encephalomyelitis. J Neuropathol Exp Neurol. 2008;67(6):532–542.
   PubMed Web of Science ®Google Scholar
• Pan H, Yao X, Chen W, Wang F, He H, Liu L, et al. Dissecting complicated viral spreading of enterovirus 71 using in situ bioorthogonal fluorescent labeling. Biomaterials. 2018;181:199–209.
   PubMed Web of Science ®Google Scholar
• Fujii K, Sudaka Y, Takashino A, Kobayashi K, Kataoka C, Suzuki T, et al. VP1 amino acid residue 145 of enterovirus 71 is a key residue for its receptor attachment and resistance to neutralizing antibody during cynomolgus monkey infection. J Virol. 2018;92:15.
   Web of Science ®Google Scholar
• Cordey S, Schibler M, L’Huillier AG, Wagner N, Gonçalves AR, Ambrosioni J, et al. Comparative analysis of viral shedding in pediatric and adult subjects with central nervous system-associated enterovirus infections from 2013 to 2015 in Switzerland. J Clin Virol. 2017;89:22–29.
   PubMed Web of Science ®Google Scholar
• Cheng HY, Huang YC, Yen TY, Hsia SH, Hsieh YC, Li CC, et al. The correlation between the presence of viremia and clinical severity in patients with enterovirus 71 infection: a multi-center cohort study. BMC Infect Dis. 2014;14:417.
   PubMed Web of Science ®Google Scholar
• Li CC, Yang MY, Chen RF, Lin TY, Tsao KC, Ning HC, et al. Clinical manifestations and laboratory assessment in an enterovirus 71 outbreak in southern Taiwan. Scand J Infect Dis. 2002;34(2):104–109.
   PubMed Web of Science ®Google Scholar
• Tan SH, Ong KC, Wong KT. Enterovirus 71 can directly infect the brainstem via cranial nerves and infection can be ameliorated by passive immunization. J Neuropathol Exp Neurol. 2014;73(11):999–1008.
   PubMed Web of Science ®Google Scholar
• Lin P, Gao L, Huang Y, Chen Q, Shen H. An enterovirus 71 strain causes skeletal muscle damage in infected mice. Int J Clin Exp Pathol. 2015;8(4):3460–3468.
   PubMed Web of Science ®Google Scholar
• Chen BS, Lee HC, Lee KM, Gong YN, Shih SR. Enterovirus and encephalitis. Front Microbiol. 2020;11:261.
   PubMed Web of Science ®Google Scholar
• Chen CS, Yao YC, Lin SC, Lee YP, Wang YF, Wang JR, et al. Retrograde axonal transport: a major transmission route of enterovirus 71 in mice. J Virol. 2007;81(17):8996–9003.
   PubMed Web of Science ®Google Scholar
• Wong KT, Munisamy B, Ong KC, Kojima H, Noriyo N, Chua KB, et al. The distribution of inflammation and virus in human enterovirus 71 encephalomyelitis suggests possible viral spread by neural pathways. J Neuropathol Exp Neurol. 2008;67(2):162–169.
   PubMed Web of Science ®Google Scholar
• Feng M, Guo S, Fan S, Zeng X, Zhang Y, Liao Y, et al. The preferential infection of astrocytes by enterovirus 71 plays a key role in the viral neurogenic pathogenesis. Front Cell Infect Microbiol. 2016;6:192.
   PubMed Web of Science ®Google Scholar
• Li H, Su L, Zhang T, He F, Yin Y. MRI reveals segmental distribution of enterovirus lesions in the central nervous system: a probable clinical evidence of retrograde axonal transport of EV-A71. J Neurovirol. 2019;25(3):354–362.
   PubMed Web of Science ®Google Scholar
• Wang W, Sun J, Wang N, Sun Z, Ma Q, Li J, et al. Enterovirus A71 capsid protein VP1 increases blood–brain barrier permeability and virus receptor vimentin on the brain endothelial cells. J Neurovirol. 2020;26(1):84–94.
   PubMed Web of Science ®Google Scholar
• Al-Obaidi MMJ, Bahadoran A, Wang SM, Manikam R, Raju CS, Sekaran SD. Disruption of the blood brain barrier is vital property of neurotropic viral infection of the central nervous system. Acta Virol. 2018;62(1):16–27.
   PubMed Web of Science ®Google Scholar
• Yang WX, Terasaki T, Shiroki K, Ohka S, Aoki J, Tanabe S, et al. Efficient delivery of circulating poliovirus to the central nervous system independently of poliovirus receptor. Virology. 1997;229(2):421–428.
   PubMed Web of Science ®Google Scholar
• Volle R, Archimbaud C, Couraud PO, Romero IA, Weksler B, Mirand A, et al. Differential permissivity of human cerebrovascular endothelial cells to enterovirus infection and specificities of serotype EV-A71 in crossing an in vitro model of the human blood-brain barrier. J Gen Virol. 2015;96(7):1682–1695.
   PubMedGoogle Scholar
• Mao L, Wu J, Shen L, Yang J, Chen J, Xu H. Enterovirus 71 transmission by exosomes establishes a productive infection in human neuroblastoma cells. Virus Genes. 2016;52(2):189–194.
   PubMed Web of Science ®Google Scholar
• Huang HI, Lin JY, Chiang HC, Huang PN, Lin QD, Shih SR. Exosomes facilitate transmission of enterovirus A71 from human intestinal epithelial cells. J Infect Dis. 2020;222(3):456–469.
   PubMed Web of Science ®Google Scholar
• Gu J, Wu J, Fang D, Qiu Y, Zou X, Jia X, et al. . Exosomes cloak the virion to transmit enterovirus 71 non-lytically. Virulence. 2020;11(1):32–38..
   PubMed Web of Science ®Google Scholar
• Gu J, Wu J, Cao Y, Zou X, Jia X, Yin Y, et al. A mouse model for infection with enterovirus A71 in small extracellular vesicles. mSphere. 2020;5(4):e00377–20.
   PubMed Web of Science ®Google Scholar
• Ayloo S, Gu C. Transcytosis at the blood-brain barrier. Curr Opin Neurol. 2019;57: 32–38.
   Google Scholar
• Lin YW, Wang SW, Tung YY, Chen SH. Enterovirus 71 infection of human dendritic cells. Exp Biol Med (Maywood). 2009;234(10):1166–1173.
   PubMed Web of Science ®Google Scholar
• Wang J, Pu J, Huang H, Zhang Y, Liu L, Yang E, et al. EV71-infected CD14(+) cells modulate the immune activity of T lymphocytes in rhesus monkeys. Emerg Microbes Infect. 2013;2(7):e44.
   PubMed Web of Science ®Google Scholar
• Wongsa A, Noulsri E, Phawong C, Puthavathana P, Tassaneetrithep B. Replication and cytokine profiles of different subgenotypes of enterovirus 71 isolated from Thai patients in peripheral blood mononuclear cells. Microb Pathog. 2019;132:215–221.
   PubMed Web of Science ®Google Scholar
• Chen KR, Yu CK, Kung SH, Chen SH, Chang CF, Ho TC, et al. Toll-like receptor 3 is involved in detection of enterovirus A71 infection and targeted by viral 2A protease. Viruses. 2018;10(12):689.
   Web of Science ®Google Scholar
• Zhu K, Yang J, Luo K, Yang C, Zhang N, Xu R, et al. TLR3 signaling in macrophages is indispensable for the protective immunity of invariant natural killer T cells against enterovirus 71 infection. PLoS Pathog. 2015;11:1.
   Web of Science ®Google Scholar
• Huang HI, Lin JY, Chen SH. EV71 Infection induces IFN-β expression in neural cells. Viruses. 2019;11:12.
   Web of Science ®Google Scholar
• Lin YL, Hu YC, Liang CC, Lin SY, Liang YC, Yuan HP, et al. Enterovirus-71 virus-like particles induce the activation and maturation of human monocyte-derived dendritic cells through TLR4 signaling. PLoS One. 2014;9:10.
   Web of Science ®Google Scholar
• Luo Z, Su R, Wang W, Liang Y, Zeng X, Shereen MA, et al. EV71 infection induces neurodegeneration via activating TLR7 signaling and IL-6 production. PLoS Pathog. 2019;15:11.
   Web of Science ®Google Scholar
• Yogarajah T, Ong KC, Perera D, Wong KT. AIM2 Inflammasome-mediated pyroptosis in enterovirus A71-infected neuronal cells restricts viral replication. Sci Rep. 2017;7(1):5845.
   PubMedGoogle Scholar
• Kuo RL, Kao LT, Lin SJ, Wang RYL, Shih SR. MDA5 plays a crucial role in enterovirus 71 RNA-mediated IRF3 activation. PLoS One. 2013;8:5.
   Google Scholar
• Lancaster KZ, Pfeiffer JK. Limited trafficking of a neurotropic virus through inefficient retrograde axonal transport and the type I interferon response. PLoS Pathog. 2010;6:3.
   Web of Science ®Google Scholar
• Luethy LN, Erickson AK, Jesudhasan PR, Ikizler M, Dermody TS, Pfeiffer JK. Comparison of three neurotropic viruses reveals differences in viral dissemination to the central nervous system. Virology. 2016;487:1–10.
   PubMed Web of Science ®Google Scholar
• Yi L, He Y, Chen Y, Kung HF, He ML. Potent inhibition of human enterovirus 71 replication by type I interferon subtypes. Antivir Ther. 2011;16(1):51–58.
   PubMed Web of Science ®Google Scholar
• Ke Y, Liu WN, Her Z, Liu M, Tan SY, Tan YW, et al. Enterovirus-A71 infection activates human immune responses and induces pathological changes in humanized mice. J Virol. 2019; 93(3) e01066-18.
   Google Scholar
• Zheng Z, Li H, Zhang Z, Meng J, Mao D, Bai B, et al. . Enterovirus 71 2C protein inhibits TNF-α–mediated activation of NF-κB by suppressing IκB kinase β phosphorylation. J Immunol. 2011;187(5):2202–2212.
   PubMed Web of Science ®Google Scholar
• Liu Y, Zhang Z, Zhao X, Yu R, Zhang X, Wu S, et al. . Enterovirus 71 inhibits cellular type I interferon signaling by downregulating JAK1 protein expression. Viral Immunol. 2014;27(6):267–276.
   PubMed Web of Science ®Google Scholar
• Good C, Wells AI, Coyne CB. Type III interferon signaling restricts enterovirus 71 infection of goblet cells. Sci Adv. 2019;5:3.
   Web of Science ®Google Scholar
• Aw-Yong KL, Nik Nadia NMN, Tan CW, Sam IC, Chan YF. Immune responses against enterovirus A71 infection: implications for vaccine success. Rev Med Virol. 2019;29:5.
   Web of Science ®Google Scholar
• Chang LY, Hsiung CA, Lu CY, Lin TY, Huang FY, Lai YH, et al. , Status of cellular rather than humoral immunity is correlated with clinical outcome of enterovirus 71. Pediatr Res. 60(4): 466–471. 2006.
   PubMed Web of Science ®Google Scholar
• Chang LY, Chang IS, Chen WJ, Huang YC, Chen GW, Shih SR, et al. . HLA-A33 is associated with susceptibility to enterovirus 71 infection. Pediatrics. 2008;122(6):1271–1276.
   PubMed Web of Science ®Google Scholar
• Li YP, Li M, Jia XL, Deng HL, Wang WJ, Wu FP, et al. Association of gene polymorphisms of pattern-recognition receptor signaling pathway with the risk and severity of hand, foot, and mouth disease caused by enterovirus 71 in Chinese Han population. J Med Virol. 2018;90(4):692–698.
   PubMed Web of Science ®Google Scholar
• Pang L, Gong X, Liu N, Xie G, Gao W, Kong G, et al. A polymorphism in melanoma differentiation-associated gene 5 may be a risk factor for enterovirus 71 infection. Clin Microbiol Infect. 2014;20(10):0711–07.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Suo X, Zhang Y. Association of IL-13, S100B, and TLR-7 gene polymorphisms with enterovirus 71 infection in hand, foot, and mouth disease in China. Genet Test Mol Biomarkers. 2019;23(3):188–196.
   PubMed Web of Science ®Google Scholar
• Zou R, Zhang G, Li S, Wang W, Yuan J, Li J, et al. A functional polymorphism in IFNAR1 gene is associated with susceptibility and severity of HFMD with EV71 infection. Sci Rep. 2015;5:1.
   Web of Science ®Google Scholar
• Eigen M. Viral quasispecies. Sci Am. 1993;269(1):42–49.
   PubMedGoogle Scholar
• Domingo E. Quasispecies theory in virology. J Virol. 2002;76(1):463–465.
   PubMed Web of Science ®Google Scholar
• Eigen M. On the nature of virus quasispecies. Trends Microbiol. 1996;4(6):216–218.
   PubMed Web of Science ®Google Scholar
• Steinhauer DA, Domingo E, Holland JJ. Lack of evidence for proofreading mechanisms associated with an RNA virus polymerase. Gene. 1992;122(2):281–288.
   PubMed Web of Science ®Google Scholar
• Domingo E, Sheldon J, Perales C. Viral quasispecies evolution. Microbiol Mol Biol Rev. 2012;76(2):159–216.
   PubMed Web of Science ®Google Scholar
• Vignuzzi M, Stone JK, Arnold JJ, Cameron CE, Andino R. Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population. Nature. 2006;439(7074):344–348.
   PubMed Web of Science ®Google Scholar
• Meng T, Kwang J. Attenuation of human enterovirus 71 high-replication-fidelity variants in AG129 mice. J Virol. 2014;88(10):5803–5815.
   PubMed Web of Science ®Google Scholar
• Pfeiffer JK, Kirkegaard K. Bottleneck-mediated quasispecies restriction during spread of an RNA virus from inoculation site to brain. Proc Natl Acad Sci USA. 2006;103(14):5520–5525.
   PubMed Web of Science ®Google Scholar
• Huang SW, Huang YH, Tsai HP, Kuo PH, Wang SM, Liu CC, et al. A selective bottleneck shapes the evolutionary mutant spectra of enterovirus A71 during viral dissemination in humans. J Virol. 2017; 91 (23): e01062-17
   Google Scholar
• Gardner CL, Ebel GD, Ryman KD, Klimstra WB. Heparan sulfate binding by natural eastern equine encephalitis viruses promotes neurovirulence. Proc Natl Acad Sci USA. 2011;108(38):16026–16031.
   PubMed Web of Science ®Google Scholar
• Lee E, Lobigs M. E protein domain III determinants of yellow fever virus 17D vaccine strain enhance binding to glycosaminoglycans, impede virus spread, and attenuate virulence. J Virol. 2008;82(12):6024–6033.
   PubMed Web of Science ®Google Scholar
• Lee E, Lobigs M. Mechanism of virulence attenuation of glycosaminoglycan-binding variants of Japanese encephalitis virus and Murray Valley encephalitis virus. J Virol. 2002;76(10):4901–4911.
   PubMed Web of Science ®Google Scholar
• Lee E, Hall RA, LobigsM. Common E protein determinants for attenuation of glycosaminoglycan-binding variants of Japanese encephalitis and West Nile viruses. J Virol. 2004;78(15):8271–8280.
   PubMed Web of Science ®Google Scholar
• Bernard KA, Klimstra WB, Johnston RE. Mutations in the E2 glycoprotein of Venezuelan equine encephalitis virus confer heparan sulfate interaction, low morbidity, and rapid clearance from blood of mice. Virology. 2000;276(1):93–103.
   PubMed Web of Science ®Google Scholar
• Wang Y, Pfeiffer JK. Emergence of a large-plaque variant in mice infected with coxsackievirus B3. mBio. 2016;7:2.
   Web of Science ®Google Scholar
• Prestwood TR, Prigozhin DM, Sharar KL, Zellweger RM, Shresta S. A mouse-passaged dengue virus strain with reduced affinity for heparan sulfate causes severe disease in mice by establishing increased systemic viral loads. J Virol. 2008;82(17):8411–8421.
   PubMed Web of Science ®Google Scholar
• Byrnes AP, Griffin DE. Large-plaque mutants of Sindbis virus show reduced binding to heparan sulfate, heightened viremia, and slower clearance from the circulation. J Virol. 2000;74(2):644–651.
   PubMed Web of Science ®Google Scholar
• Gardner CL, Choi-Nurvitadhi J, Sun C, Bayer A, Hritz J, Ryman KD, et al. Natural variation in the heparan sulfate binding domain of the eastern equine encephalitis virus E2 glycoprotein alters interactions with cell surfaces and virulence in mice. J Virol. 2013;87(15):8582–8590.
   PubMed Web of Science ®Google Scholar
• Reddi HV, Kumar AS, Kung AY, Kallio PD, Schlitt BP, Lipton HL. Heparan sulfate-independent infection attenuates high-neurovirulence GDVII virus-induced encephalitis. J Virol. 2004;78(16):8909–8916.
   PubMed Web of Science ®Google Scholar
• Racaniello VR. One hundred years of poliovirus pathogenesis. Virology. 2006;344(1):9–16.
   PubMed Web of Science ®Google Scholar
• Schieble JH, Fox VL, Lennette EH. A probable new human picornavirus associated with respiratory diseases. Am J Epidemiol. 1967;85(2):297–310.
   PubMed Web of Science ®Google Scholar
• Esposito S, Bosis S, Niesters H, Principi N. Enterovirus D68 Infection. Viruses. 2015;7(11):6043–6050.
   PubMed Web of Science ®Google Scholar
• Holm-Hansen CC, Midgley SE, Fischer TK. Global emergence of enterovirus D68: a systematic review. Lancet Infect Dis. 2016;16(5):e64–e75.
   PubMed Web of Science ®Google Scholar
• Ohka S, Nomoto A. Recent insights into poliovirus pathogenesis. Trends Microbiol. 2001;9(10):501–506.
   PubMed Web of Science ®Google Scholar
• Imamura T, Okamoto M, Nakakita S, Suzuki A, Saito M, Tamaki R, et al. . Antigenic and receptor binding properties of enterovirus 68. J Virol. 2014;88(5):2374–2384.
   PubMed Web of Science ®Google Scholar
• Wei W, Guo H, Chang J, Yu Y, Liu G, Zhang N, et al. . ICAM-5/Telencephalin is a functional entry receptor for enterovirus D68. Cell Host Microbe. 2016;20(5):631–641.
   PubMed Web of Science ®Google Scholar
• Ren R, Racaniello VR. Poliovirus spreads from muscle to the central nervous system by neural pathways. J Infect Dis. 1992;166(4):747–752.
   PubMed Web of Science ®Google Scholar
• Ohka S, Yang WX, Terada E, Iwasaki K, Nomoto A. Retrograde transport of intact poliovirus through the axon via the fast transport system. Virology. 1998;250(1):67–75.
   PubMed Web of Science ®Google Scholar
• Pfeiffer JK. Innate host barriers to viral trafficking and population diversity: lessons learned from poliovirus. Adv Virus Res. 2010;77:85–118.
   PubMed Web of Science ®Google Scholar
• Oberste MS, Maher K, Schnurr D, Flemister MR, Lovchik JC, Peters H, et al. . Enterovirus 68 is associated with respiratory illness and shares biological features with both the enteroviruses and the rhinoviruses. J Gen Virol. 2004;85(9):2577–2584.
   PubMedGoogle Scholar
• Hixon AM, Clarke P, Tyler KL. Contemporary circulating enterovirus D68 strains infect and undergo retrograde axonal transport in spinal motor neurons independent of sialic acid. J Virol. 2019;93(16): e00578-19.
   Google Scholar
• Luo Z, Ge M, Chen J, Geng Q, Tian M, Qiao Z, et al. . HRS plays an important role for TLR7 signaling to orchestrate inflammation and innate immunity upon EV71 infection. PLoS Pathog. 2017;13:8.
   Web of Science ®Google Scholar
• Wang CY, Huang AC, Hour MJ, Huang SH, Kung SH, Chen CH, et al. . Antiviral potential of a novel compound CW-33 against enterovirus A71 via inhibition of viral 2A protease. Viruses. 2015;7(6):3155–3171.
   PubMed Web of Science ®Google Scholar
• Visser LJ, Langereis MA, Rabouw HH, Wahedi M, Muntjewerff EM, de Groot RJ, et al. . Essential role of enterovirus 2A protease in counteracting stress granule formation and the induction of type I interferon. J Virol. 2019 93(10): e00222-19
   Google Scholar
• Lei X, Han N, Xiao X, Jin Q, He B, Wang J. Enterovirus 71 3C inhibits cytokine expression through cleavage of the TAK1/TAB1/TAB2/TAB3 complex. J Virol. 2014;88(17):9830–9841.
   PubMed Web of Science ®Google Scholar
• Lei X, Liu X, Ma Y, Sun Z, Yang Y, Jin Q, et al. . The 3C protein of enterovirus 71 inhibits retinoid acid-inducible gene I-mediated interferon regulatory factor 3 activation and type I interferon responses. J Virol. 2010;84(16):8051–8061.
   PubMed Web of Science ®Google Scholar
• Lei X, Xiao X, Xue Q, Jin Q, He B, Wang J. Cleavage of interferon regulatory factor 7 by enterovirus 71 3C suppresses cellular responses. J Virol. 2013;87(3):1690–1698.
   PubMed Web of Science ®Google Scholar
• Lei X, Sun Z, Liu X, Jin Q, He B, Wang J. Cleavage of the adaptor protein TRIF by enterovirus 71 3C inhibits antiviral responses mediated by Toll-like receptor 3. J Virol. 2011;85(17):8811–8818.
   PubMed Web of Science ®Google Scholar
• Du H, Yin P, Yang X, Zhang L, Jin Q, Zhu G. Enterovirus 71 2C protein inhibits NF-κB activation by binding to Rel A (p65). Sci Rep. 2015;5.
   Web of Science ®Google Scholar
• Wang B, Xi X, Lei X, Zhang X, Cui S, Wang J, et al. . Enterovirus 71 protease 2A pro targets MAVS to inhibit anti-viral type I interferon responses. PLoS Pathog. 2013;9:3.
   Web of Science ®Google Scholar
• Ida-Hosonuma M, Iwasaki T, Yoshikawa T, Nagata N, Sato Y, Sata T, et al. . The alpha/beta interferon response controls tissue tropism and pathogenicity of poliovirus. J Virol. 2005;79(7):4460–4469.
   PubMed Web of Science ®Google Scholar
• Fiette L, Aubert C, Müller U, Huang S, Aguet M, Brahic M, et al. . Theiler’s virus infection of 129Sv mice that lack the interferon alpha/beta or interferon gamma receptors. J Exp Med. 1995;181(6):2069–2076.
   PubMed Web of Science ®Google Scholar
• Kuss SK, Etheredge CA, Pfeiffer JK. Multiple host barriers restrict poliovirus trafficking in mice. PLoS Pathog. 2008;4:6.
   Web of Science ®Google Scholar
• Xiang Z, Wang J. . Enterovirus D68 and human respiratory infections. Semin Respir Crit Care Med. 2016;37(4):578–585.
   PubMed Web of Science ®Google Scholar
• Sun J, Hu XY, Yu XF. Current understanding of human enterovirus D68. Viruses. 2019;11:6.
   Web of Science ®Google Scholar
• Xiang Z, Li L, Lei X, Zhou H, Zhou Z, He B, et al. . Enterovirus 68 3C protease cleaves TRIF to attenuate antiviral responses mediated by Toll-like receptor 3. J Virol. 2014;88(12):6650–6659.
   PubMed Web of Science ®Google Scholar
• Shindarov LM, Chumakov MP, Voroshilova MK, Bojinov S, Vasilenko SM, Iordanov I, et al. Epidemiological, clinical, and pathomorphological characteristics of epidemic poliomyelitis-like disease caused by enterovirus 71. J Hyg Epidemiol Microbiol Immunol. 1979;23(3):284–295.
   PubMedGoogle Scholar
• Ooi MH, Wong SC, Podin Y, Akin W, Del Sel S, Mohan A, et al. . Human enterovirus 71 disease in Sarawak, Malaysia: a prospective clinical, virological, and molecular epidemiological study. Clin Infect Dis. 2007;44(5):646–656.
   PubMed Web of Science ®Google Scholar
• Zhou Y, Tan LV, Luo K, Liao Q, Wang L, Qiu Q. et al. . Genetic variation of multiple serotypes of enteroviruses associated with hand, foot and mouth disease in Southern China. Virol Sin(preprint). 2020; 1–14.
   Google Scholar
• Chua BH, Phuektes P, Sanders SA, Nicholls PK, McMinn PC. The molecular basis of mouse adaptation by human enterovirus 71. J Gen Virol. 2008;89(7):1622–1632.
   PubMedGoogle Scholar
• Caine EA, Moncla LH, Ronderos MD, Friedrich TC, Osorio JE. A single mutation in the VP1 of enterovirus 71 is responsible for increased virulence and neurotropism in adult interferon-deficient mice. J Virol. 2016;90(19):8592–8604.
   PubMed Web of Science ®Google Scholar
• Van der Sanden SMG, Sachs N, Koekkoek SM, Koen G, Pajkrt D, Clevers H, et al. . Enterovirus 71 infection of human airway organoids reveals VP1-145 as a viral infectivity determinant. Emerg Microbes Infect. 2018;7(1):84.
   PubMedGoogle Scholar
• Jiao XY, Guo L, Huang DY, Chang XL, Qiu QC. Distribution of EV71 receptors SCARB2 and PSGL-1 in human tissues. Virus Res. 2014;190:40–52.
   PubMed Web of Science ®Google Scholar
• Yu P, Gao Z, Zong Y, Bao L, Xu L, Deng W, et al. Histopathological features and distribution of EV71 antigens and SCARB2 in human fatal cases and a mouse model of enterovirus 71 infection. Virus Res. 2014;189:121–132.
   PubMed Web of Science ®Google Scholar
• Kobayashi K, Sudaka Y, Takashino A, Imura A, Fujii K, Koike S. Amino acid variation at VP1-145 of enterovirus 71 determines attachment receptor usage and neurovirulence in human scavenger receptor B2 transgenic mice. J Virol. 2018; 92(15):e00681-18
   Google Scholar
• Caine EA, Osorio JE. In vivo imaging with bioluminescent enterovirus 71 allows for real-time visualization of tissue tropism and viral spread. J Virol. 2017;91(5):e01759-16
   Google Scholar
• Sin J, Mangale V, Thienphrapa W, Gottlieb RA, Feuer R. Recent progress in understanding coxsackievirus replication, dissemination, and pathogenesis. Virology. 2015;484:288–304.
   PubMed Web of Science ®Google Scholar
• Van Riel D, Verdijk R, Kuiken T. The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system . J Pathol. 2015;235(2):277–287.
   PubMed Web of Science ®Google Scholar
• Huang HI, Lin JY, Chen HH, Yeh SB, Kuo RL, Weng KF, et al. Enterovirus 71 infects brain-derived neural progenitor cells. Virology. 2014;468-470:592–600.
   PubMed Web of Science ®Google Scholar
• Tan CW, Lai JK, Sam IC, Chan YF. Recent developments in antiviral agents against enterovirus 71 infection. J Biomed Sci. 2014;21:14.
   PubMed Web of Science ®Google Scholar
• Lin JY, Kung YA, Shih SR. Antivirals and vaccines for enterovirus A71. J Biomed Sci. 2019;26(1):65.
   PubMed Web of Science ®Google Scholar
• Lim ZQ, Ng QY, Ng JWQ, Mahendran V, Alonso S. Recent progress and challenges in drug development to fight hand, foot and mouth disease. Expert Opin Drug Discov. 2020;15(3):359–371.
   PubMed Web of Science ®Google Scholar
• Wang SM, Lei HY, Huang MC, Wu JM, Chen CT, Wang JN, et al. Therapeutic efficacy of milrinone in the management of enterovirus 71-induced pulmonary oedema. Pediatr Pulmonol. 2005;39(3):219–223.
   PubMed Web of Science ®Google Scholar
• Chi CY, Khanh TH, Thoa le PK, Tseng FC, Wang SM, Thinh le Q, et al. Milrinone therapy for enterovirus 71-induced pulmonary oedema and/or neurogenic shock in children: a randomized controlled trial. Crit Care Med. 1754-60;41(7):2013.
   Google Scholar
• He Y, Yang J, Zeng G, Shen T, Fontaine RE, Zhang L, et al. Risk factors for critical disease and death from hand, foot and mouth disease. Pediatr Infect Dis J. 2014;33(9):966–970.
   PubMed Web of Science ®Google Scholar
• World Health Organization. Severe complications of hand, foot and mouth disease (HFMD) caused by EV-71 in Cambodia – conclusion of the joint investigation. 13 Jul 2012; Sect. Disease Outbreak News 2012.
   Google Scholar
• Chea S, Cheng YB, Chokephaibulkit K, Chotpitayasunondh T, Rogier van Doorn H, Hafy Z, et al. Workshop on use of intravenous immunoglobulin in hand, foot and mouth disease in Southeast Asia. Emerg Infect Dis. 2015;21:1.
   PubMedGoogle Scholar
• Wang SM, Lei HY, Huang MC, Su LY, Lin HC, Yu CK, et al. Modulation of cytokine production by intravenous immunoglobulin in patients with enterovirus 71-associated brainstem encephalitis. J Clin Virol. 2006;37(1):47–52.
   PubMed Web of Science ®Google Scholar
• Pascual-Goñi E, Josa M, Launes C, Querol L, Del Cuerpo M, Bosch MA, et al. . Excellent response to plasma exchange in three patients with enterovirus-71 neurological disease. Front Neurol. 2019;10:548.
   PubMed Web of Science ®Google Scholar
• Zhang D, Chen J, Ba-Thein W. Hand-foot-mouth disease and use of steroids, intravenous immunoglobulin, and traditional Chinese herbs in a tertiary hospital in Shantou, China. BMC Complement Altern Med. 2018;18(1):190.
   PubMedGoogle Scholar
• Liu ML, Lee YP, Wang YF, Lei HY, Liu CC, Wang SM, et al. Type I interferons protect mice against enterovirus 71 infection. J Gen Virol. 2005;86(12):3263–3269.
   PubMedGoogle Scholar
• Hung HC, Wang HC, Shih SR, Teng IF, Tseng CP, Hsu JTA. Synergistic inhibition of enterovirus 71 replication by interferon and rupintrivir. J Infect Dis. 2011;203(12):1784–1790.
   PubMed Web of Science ®Google Scholar
• Ren P, Zou G, Bailly B, Xu S, Zeng M, Chen X, et al. The approved pediatric drug suramin identified as a clinical candidate for the treatment of EV71 infection - suramin inhibits EV71 infection in vitro and in vivo. Emerg Microbes Infect. 2014; 3(9): e62.
   Google Scholar
• Lanko K, Shi C, Patil S, Delang L, Matthijnssens J, Mirabelli C, et al. Assessing the in vitro resistance development in enterovirus 71 in the context of combination antiviral treatment. bioRxiv. 2020.
   Google Scholar
• Ren P, Zheng Y, Wang W, Hong L, Delpeyroux F, Arenzana-Seisdedos F, et al. Suramin interacts with the positively charged region surrounding the 5-fold axis of the EV-A71 capsid and inhibits multiple enterovirus A. Sci Rep. 2017; 7:42902.
   Google Scholar
• Le RQ, Li L, Yuan W, Shord SS, Nie L, Habtemariam BA, et al. FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome. Oncologist 2018;23(8):943–947.
   PubMed Web of Science ®Google Scholar