{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:57:35Z","timestamp":1790517455094,"version":"4.1.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,4,27]],"date-time":"2018-04-27T00:00:00Z","timestamp":1524787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,4,27]],"date-time":"2018-04-27T00:00:00Z","timestamp":1524787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Enterovirus 71 (EV71) is a major cause of hand, foot and mouth disease (HFMD). The current EV71 propagating in Vero (EV-V) or sub-passaged in RD (EV-R) cells was used as a pathogen. Interestingly, EV-R exhibited differential virulence; challenging human scavenger receptor class B2-expressing (hSCARB2-Tg) mice with EV71 revealed that EV-V was more virulent than EV-R: 100% of mice that received lethal amounts of EV-V died, while all the mice that received EV-R survived. Severe pathogenesis correlated with viral burdens and proinflammatory cytokine levels were observed in EV-V-challenged mice, but controversy in EV-R-challenged mice. Consensus sequence analysis revealed EV-R rapidly acquired complete mutations at E145G and S241L and partial mutations at V146I of VP1, and acquired a T to C substitution at nucleotide 494 of the 5\u2032-UTR. EV-R exhibited higher binding affinity for another EV71 receptor, human P-selectin glycoprotein ligand-1 (hPSGL-1), than EV-V. Both EV71s exhibited no significant difference in binding to hSCARB2. The molecular modelling indicate that these mutations might influence EV71 engagement with PSGL-1 and <jats:italic>in vivo<\/jats:italic> virulence.<\/jats:p>","DOI":"10.1038\/s41598-018-25091-7","type":"journal-article","created":{"date-parts":[[2018,4,23]],"date-time":"2018-04-23T15:24:18Z","timestamp":1524497058000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Mutations in VP1 and 5\u2032-UTR affect enterovirus 71 virulence"],"prefix":"10.1038","volume":"8","author":[{"given":"Ching-Kun","family":"Chang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang-Rung","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Chin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuen-Jin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nai-Hsiang","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ju","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Ling","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Chyi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Hung","family":"Chow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,4,27]]},"reference":[{"key":"25091_CR1","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1056\/NEJM199909233411301","volume":"341","author":"M Ho","year":"1999","unstructured":"Ho, M. et al. An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group. N Engl J Med 341, 929\u2013935 (1999).","journal-title":"N Engl J Med"},{"key":"25091_CR2","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1086\/520149","volume":"29","author":"SM Wang","year":"1999","unstructured":"Wang, S. M. et al. Clinical spectrum of enterovirus 71 infection in children in southern Taiwan, with an emphasis on neurological complications. Clin Infect Dis 29, 184\u2013190 (1999).","journal-title":"Clin Infect Dis"},{"key":"25091_CR3","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S1386-6532(00)00068-8","volume":"17","author":"CC Liu","year":"2000","unstructured":"Liu, C. C., Tseng, H. W., Wang, S. M., Wang, J. R. & Su, I. J. An outbreak of enterovirus 71 infection in Taiwan, 1998: epidemiologic and clinical manifestations. J Clin Virol 17, 23\u201330 (2000).","journal-title":"J Clin Virol"},{"key":"25091_CR4","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1086\/521895","volume":"45","author":"CM Perez-Velez","year":"2007","unstructured":"Perez-Velez, C. M. et al. Outbreak of neurologic enterovirus type 71 disease: a diagnostic challenge. Clin Infect Dis 45, 950\u2013957 (2007).","journal-title":"Clin Infect Dis"},{"key":"25091_CR5","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1056\/NEJM199909233411302","volume":"341","author":"CC Huang","year":"1999","unstructured":"Huang, C. C. et al. Neurologic complications in children with enterovirus 71 infection. N Engl J Med 341, 936\u2013942, https:\/\/doi.org\/10.1056\/NEJM199909233411302 (1999).","journal-title":"N Engl J Med"},{"key":"25091_CR6","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1038\/nm.1961","volume":"15","author":"Y Nishimura","year":"2009","unstructured":"Nishimura, Y. et al. Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71. Nat Med 15, 794\u2013797, https:\/\/doi.org\/10.1038\/nm1961 (2009).","journal-title":"Nat Med"},{"key":"25091_CR7","doi-asserted-by":"publisher","first-page":"e53","DOI":"10.1038\/emi.2014.49","volume":"3","author":"S Yamayoshi","year":"2014","unstructured":"Yamayoshi, S., Fujii, K. & Koike, S. Receptors for enterovirus 71. Emerging microbes & infections 3, e53, https:\/\/doi.org\/10.1038\/emi.2014.49 (2014).","journal-title":"Emerging microbes & infections"},{"key":"25091_CR8","doi-asserted-by":"publisher","unstructured":"van der Sanden, S., Koopmans, M., Uslu, G. & van der Avoort, H. Epidemiology of Enterovirus 71 in the Netherlands, 1963\u20132008. J Clin Microbiol, https:\/\/doi.org\/10.1128\/JCM.00507-09 (2009).","DOI":"10.1128\/JCM.00507-09"},{"key":"25091_CR9","doi-asserted-by":"publisher","first-page":"e90624","DOI":"10.1371\/journal.pone.0090624","volume":"9","author":"M Bessaud","year":"2014","unstructured":"Bessaud, M. et al. Molecular comparison and evolutionary analyses of VP1 nucleotide sequences of new African human enterovirus 71 isolates reveal a wide genetic diversity. PLoS One 9, e90624, https:\/\/doi.org\/10.1371\/journal.pone.0090624 (2014).","journal-title":"PLoS One"},{"key":"25091_CR10","doi-asserted-by":"publisher","first-page":"e77133","DOI":"10.1371\/journal.pone.0077133","volume":"8","author":"YL Tsou","year":"2013","unstructured":"Tsou, Y. L. et al. Heat shock protein 90: role in enterovirus 71 entry and assembly and potential target for therapy. PLoS One 8, e77133, https:\/\/doi.org\/10.1371\/journal.pone.0077133 (2013).","journal-title":"PLoS One"},{"key":"25091_CR11","doi-asserted-by":"publisher","unstructured":"Yamayoshi, S. et al. Scavenger receptor B2 is a cellular receptor for enterovirus 71. Nat Med 15, 798\u2013801, https:\/\/doi.org\/10.1038\/nm.1992 (2009).","DOI":"10.1038\/nm.1992"},{"key":"25091_CR12","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1111\/j.1574-6976.2002.tb00601.x","volume":"26","author":"PC McMinn","year":"2002","unstructured":"McMinn, P. C. An overview of the evolution of enterovirus 71 and its clinical and public health significance. FEMS Microbiol Rev 26, 91\u2013107 (2002).","journal-title":"FEMS Microbiol Rev"},{"key":"25091_CR13","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1038\/nsmb.2255","volume":"19","author":"X Wang","year":"2012","unstructured":"Wang, X. et al. A sensor-adaptor mechanism for enterovirus uncoating from structures of EV71. Nat Struct Mol Biol 19, 424\u2013429, https:\/\/doi.org\/10.1038\/nsmb.2255 (2012).","journal-title":"Nat Struct Mol Biol"},{"key":"25091_CR14","doi-asserted-by":"publisher","first-page":"e57591","DOI":"10.1371\/journal.pone.0057591","volume":"8","author":"YW Lin","year":"2013","unstructured":"Lin, Y. W. et al. Human SCARB2 transgenic mice as an infectious animal model for enterovirus 71. PLoS One 8, e57591, https:\/\/doi.org\/10.1371\/journal.pone.0057591 (2013).","journal-title":"PLoS One"},{"key":"25091_CR15","doi-asserted-by":"publisher","first-page":"10384","DOI":"10.1128\/JVI.01083-09","volume":"83","author":"G Anez","year":"2009","unstructured":"Anez, G., Men, R., Eckels, K. H. & Lai, C. J. Passage of dengue virus type 4 vaccine candidates in fetal rhesus lung cells selects heparin-sensitive variants that result in loss of infectivity and immunogenicity in rhesus macaques. J Virol 83, 10384\u201310394, https:\/\/doi.org\/10.1128\/JVI.01083-09 (2009).","journal-title":"J Virol"},{"key":"25091_CR16","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1128\/JVI.02482-15","volume":"90","author":"S Yuan","year":"2015","unstructured":"Yuan, S. et al. Identification of Positively Charged Residues in Enterovirus 71 Capsid Protein VP1 Essential for Production of Infectious Particles. J Virol 90, 741\u2013752, https:\/\/doi.org\/10.1128\/JVI.02482-15 (2015).","journal-title":"J Virol"},{"key":"25091_CR17","doi-asserted-by":"publisher","first-page":"e1003511","DOI":"10.1371\/journal.ppat.1003511","volume":"9","author":"Y Nishimura","year":"2013","unstructured":"Nishimura, Y. et al. Enterovirus 71 binding to PSGL-1 on leukocytes: VP1-145 acts as a molecular switch to control receptor interaction. PLoS pathogens 9, e1003511, https:\/\/doi.org\/10.1371\/journal.ppat.1003511 (2013).","journal-title":"PLoS pathogens"},{"key":"25091_CR18","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.virol.2011.10.015","volume":"422","author":"SW Huang","year":"2012","unstructured":"Huang, S. W., Wang, Y. F., Yu, C. K., Su, I. J. & Wang, J. R. Mutations in VP2 and VP1 capsid proteins increase infectivity and mouse lethality of enterovirus 71 by virus binding and RNA accumulation enhancement. Virology 422, 132\u2013143, https:\/\/doi.org\/10.1016\/j.virol.2011.10.015 (2012).","journal-title":"Virology"},{"key":"25091_CR19","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.1099\/vir.0.043893-0","volume":"93","author":"Z Zaini","year":"2012","unstructured":"Zaini, Z. & McMinn, P. A single mutation in capsid protein VP1 (Q145E) of a genogroup C4 strain of human enterovirus 71 generates a mouse-virulent phenotype. J Gen Virol 93, 1935\u20131940, https:\/\/doi.org\/10.1099\/vir.0.043893-0 (2012).","journal-title":"J Gen Virol"},{"key":"25091_CR20","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.micinf.2011.04.004","volume":"13","author":"W Wang","year":"2011","unstructured":"Wang, W. et al. A mouse muscle-adapted enterovirus 71 strain with increased virulence in mice. Microbes and infection\/Institut Pasteur 13, 862\u2013870, https:\/\/doi.org\/10.1016\/j.micinf.2011.04.004 (2011).","journal-title":"Microbes and infection\/Institut Pasteur"},{"key":"25091_CR21","doi-asserted-by":"publisher","first-page":"3153","DOI":"10.1016\/j.vaccine.2009.03.060","volume":"27","author":"K Mizuta","year":"2009","unstructured":"Mizuta, K. et al. Cross-antigenicity among EV71 strains from different genogroups isolated in Yamagata, Japan, between 1990 and 2007. Vaccine 27, 3153\u20133158, https:\/\/doi.org\/10.1016\/j.vaccine.2009.03.060 (2009).","journal-title":"Vaccine"},{"key":"25091_CR22","doi-asserted-by":"publisher","first-page":"3653","DOI":"10.1128\/JCM.00630-09","volume":"47","author":"SW Huang","year":"2009","unstructured":"Huang, S. W. et al. Reemergence of enterovirus 71 in 2008 in taiwan: dynamics of genetic and antigenic evolution from 1998 to 2008. J Clin Microbiol 47, 3653\u20133662 (2009).","journal-title":"J Clin Microbiol"},{"key":"25091_CR23","doi-asserted-by":"publisher","first-page":"e1002826","DOI":"10.1371\/journal.ppat.1002826","volume":"8","author":"S Cordey","year":"2012","unstructured":"Cordey, S. et al. Identification of site-specific adaptations conferring increased neural cell tropism during human enterovirus 71 infection. PLoS pathogens 8, e1002826, https:\/\/doi.org\/10.1371\/journal.ppat.1002826 (2012).","journal-title":"PLoS pathogens"},{"key":"25091_CR24","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1002\/jmv.23287","volume":"84","author":"SC Chang","year":"2012","unstructured":"Chang, S. C. et al. Genetic characterization of enterovirus 71 isolated from patients with severe disease by comparative analysis of complete genomes. J Med Virol 84, 931\u2013939, https:\/\/doi.org\/10.1002\/jmv.23287 (2012).","journal-title":"J Med Virol"},{"key":"25091_CR25","doi-asserted-by":"publisher","first-page":"e26237","DOI":"10.1371\/journal.pone.0026237","volume":"6","author":"R Li","year":"2011","unstructured":"Li, R., Zou, Q., Chen, L., Zhang, H. & Wang, Y. Molecular analysis of virulent determinants of enterovirus 71. PLoS One 6, e26237, https:\/\/doi.org\/10.1371\/journal.pone.0026237 (2011).","journal-title":"PLoS One"},{"key":"25091_CR26","doi-asserted-by":"publisher","first-page":"3523","DOI":"10.1128\/AAC.48.9.3523-3529.2004","volume":"48","author":"SR Shih","year":"2004","unstructured":"Shih, S. R. et al. Mutation in enterovirus 71 capsid protein VP1 confers resistance to the inhibitory effects of pyridyl imidazolidinone. Antimicrobial agents and chemotherapy 48, 3523\u20133529, https:\/\/doi.org\/10.1128\/AAC.48.9.3523-3529.2004 (2004).","journal-title":"Antimicrobial agents and chemotherapy"},{"key":"25091_CR27","doi-asserted-by":"publisher","first-page":"2518","DOI":"10.1099\/vir.0.2008\/002915-0","volume":"89","author":"M Arita","year":"2008","unstructured":"Arita, M., Wakita, T. & Shimizu, H. Characterization of pharmacologically active compounds that inhibit poliovirus and enterovirus 71 infectivity. J Gen Virol 89, 2518\u20132530, https:\/\/doi.org\/10.1099\/vir.0.2008\/002915-0 (2008).","journal-title":"J Gen Virol"},{"key":"25091_CR28","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.antiviral.2015.10.006","volume":"124","author":"JT Kelly","year":"2015","unstructured":"Kelly, J. T. et al. Potent antiviral agents fail to elicit genetically-stable resistance mutations in either enterovirus 71 or Coxsackievirus A16. Antiviral Res 124, 77\u201382, https:\/\/doi.org\/10.1016\/j.antiviral.2015.10.006 (2015).","journal-title":"Antiviral Res"},{"key":"25091_CR29","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1128\/JVI.78.3.1393-1402.2004","volume":"78","author":"KE Murray","year":"2004","unstructured":"Murray, K. E., Steil, B. P., Roberts, A. W. & Barton, D. J. Replication of poliovirus RNA with complete internal ribosome entry site deletions. J Virol 78, 1393\u20131402 (2004).","journal-title":"J Virol"},{"key":"25091_CR30","doi-asserted-by":"publisher","first-page":"2219","DOI":"10.1128\/JVI.74.5.2219-2226.2000","volume":"74","author":"AV Gamarnik","year":"2000","unstructured":"Gamarnik, A. V. & Andino, R. Interactions of viral protein 3CD and poly(rC) binding protein with the 5\u2032 untranslated region of the poliovirus genome. J Virol 74, 2219\u20132226 (2000).","journal-title":"J Virol"},{"key":"25091_CR31","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1016\/j.micinf.2004.03.001","volume":"6","author":"KM Bedard","year":"2004","unstructured":"Bedard, K. M. & Semler, B. L. Regulation of picornavirus gene expression. Microbes and infection\/Institut Pasteur 6, 702\u2013713, https:\/\/doi.org\/10.1016\/j.micinf.2004.03.001 (2004).","journal-title":"Microbes and infection\/Institut Pasteur"},{"key":"25091_CR32","doi-asserted-by":"publisher","first-page":"e87491","DOI":"10.1371\/journal.pone.0087491","volume":"9","author":"Z Luo","year":"2014","unstructured":"Luo, Z. et al. PolyC-binding protein 1 interacts with 5\u2032-untranslated region of enterovirus 71 RNA in membrane-associated complex to facilitate viral replication. PLoS One 9, e87491, https:\/\/doi.org\/10.1371\/journal.pone.0087491 (2014).","journal-title":"PLoS One"},{"key":"25091_CR33","doi-asserted-by":"publisher","first-page":"e27082","DOI":"10.1371\/journal.pone.0027082","volume":"6","author":"MT Yeh","year":"2011","unstructured":"Yeh, M. T. et al. A single nucleotide in stem loop II of 5\u2032-untranslated region contributes to virulence of enterovirus 71 in mice. PLoS One 6, e27082, https:\/\/doi.org\/10.1371\/journal.pone.0027082 (2011).","journal-title":"PLoS One"},{"key":"25091_CR34","doi-asserted-by":"publisher","first-page":"6106","DOI":"10.1128\/JVI.02476-08","volume":"83","author":"JY Lin","year":"2009","unstructured":"Lin, J. Y. et al. hnRNP A1 interacts with the 5\u2032 untranslated regions of enterovirus 71 and Sindbis virus RNA and is required for viral replication. J Virol 83, 6106\u20136114, https:\/\/doi.org\/10.1128\/JVI.02476-08 (2009).","journal-title":"J Virol"},{"key":"25091_CR35","doi-asserted-by":"publisher","first-page":"e30507","DOI":"10.1371\/journal.pone.0030507","volume":"7","author":"YW Lin","year":"2012","unstructured":"Lin, Y. W. et al. Human SCARB2-mediated entry and endocytosis of EV71. PLoS One 7, e30507, https:\/\/doi.org\/10.1371\/journal.pone.0030507PONE-D-11-13263 (2012).","journal-title":"PLoS One"},{"key":"25091_CR36","doi-asserted-by":"publisher","first-page":"3858","DOI":"10.1016\/j.vaccine.2004.05.037","volume":"22","author":"SC Wu","year":"2004","unstructured":"Wu, S. C., Liu, C. C. & Lian, W. C. Optimization of microcarrier cell culture process for the inactivated enterovirus type 71 vaccine development. Vaccine 22, 3858\u20133864 (2004).","journal-title":"Vaccine"},{"key":"25091_CR37","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.vaccine.2006.06.083","volume":"25","author":"CC Liu","year":"2007","unstructured":"Liu, C. C., Lian, W. C., Butler, M. & Wu, S. C. High immunogenic enterovirus 71 strain and its production using serum-free microcarrier Vero cell culture. Vaccine 25, 19\u201324 (2007).","journal-title":"Vaccine"},{"key":"25091_CR38","doi-asserted-by":"publisher","first-page":"4362","DOI":"10.1016\/j.vaccine.2011.04.010","volume":"29","author":"CC Liu","year":"2011","unstructured":"Liu, C. C. et al. Identification and characterization of a cross-neutralization epitope of Enterovirus 71. Vaccine 29, 4362\u20134372 (2011).","journal-title":"Vaccine"},{"key":"25091_CR39","doi-asserted-by":"publisher","first-page":"7637","DOI":"10.1128\/JVI.03519-12","volume":"87","author":"JO Cifuente","year":"2013","unstructured":"Cifuente, J. O. et al. Structures of the procapsid and mature virion of enterovirus 71 strain 1095. J Virol 87, 7637\u20137645, https:\/\/doi.org\/10.1128\/JVI.03519-12 (2013).","journal-title":"J Virol"},{"key":"25091_CR40","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1186\/1743-422X-10-250","volume":"10","author":"X Li","year":"2013","unstructured":"Li, X. et al. Establishment of cell lines with increased susceptibility to EV71\/CA16 by stable overexpression of SCARB2. Virol J 10, 250, https:\/\/doi.org\/10.1186\/1743-422X-10-250 (2013).","journal-title":"Virol J"},{"key":"25091_CR41","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1086\/345905","volume":"36","author":"TY Lin","year":"2003","unstructured":"Lin, T. Y., Hsia, S. H., Huang, Y. C., Wu, C. T. & Chang, L. Y. Proinflammatory cytokine reactions in enterovirus 71 infections of the central nervous system. Clin Infect Dis 36, 269\u2013274 (2003).","journal-title":"Clin Infect Dis"},{"key":"25091_CR42","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1086\/376998","volume":"188","author":"SM Wang","year":"2003","unstructured":"Wang, S. M. et al. Pathogenesis of enterovirus 71 brainstem encephalitis in pediatric patients: roles of cytokines and cellular immune activation in patients with pulmonary edema. J Infect Dis 188, 564\u2013570 (2003).","journal-title":"J Infect Dis"},{"key":"25091_CR43","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1086\/591462","volume":"198","author":"SM Wang","year":"2008","unstructured":"Wang, S. M. et al. Acute chemokine response in the blood and cerebrospinal fluid of children with enterovirus 71-associated brainstem encephalitis. J Infect Dis 198, 1002\u20131006 (2008).","journal-title":"J Infect Dis"},{"key":"25091_CR44","doi-asserted-by":"publisher","first-page":"3114","DOI":"10.1128\/JVI.03029-13","volume":"88","author":"K Lyu","year":"2014","unstructured":"Lyu, K. et al. Human enterovirus 71 uncoating captured at atomic resolution. J Virol 88, 3114\u20133126, https:\/\/doi.org\/10.1128\/JVI.03029-13 (2014).","journal-title":"J Virol"},{"key":"25091_CR45","doi-asserted-by":"publisher","first-page":"6406","DOI":"10.1074\/jbc.M111.301622","volume":"287","author":"P Chen","year":"2012","unstructured":"Chen, P. et al. Molecular determinants of enterovirus 71 viral entry: cleft around GLN-172 on VP1 protein interacts with variable region on scavenge receptor B 2. J Biol Chem 287, 6406\u20136420, https:\/\/doi.org\/10.1074\/jbc.M111.301622 (2012).","journal-title":"J Biol Chem"},{"key":"25091_CR46","doi-asserted-by":"publisher","first-page":"3335","DOI":"10.1128\/JVI.02070-12","volume":"87","author":"S Yamayoshi","year":"2013","unstructured":"Yamayoshi, S., Ohka, S., Fujii, K. & Koike, S. Functional comparison of SCARB2 and PSGL1 as receptors for enterovirus 71. J Virol 87, 3335\u20133347, https:\/\/doi.org\/10.1128\/JVI.02070-12 (2013).","journal-title":"J Virol"},{"key":"25091_CR47","doi-asserted-by":"publisher","first-page":"9064","DOI":"10.1128\/JVI.00573-13","volume":"87","author":"HY Lin","year":"2013","unstructured":"Lin, H. Y. et al. Caveolar endocytosis is required for human PSGL-1-mediated enterovirus 71 infection. J Virol 87, 9064\u20139076, https:\/\/doi.org\/10.1128\/JVI.00573-13 (2013).","journal-title":"J Virol"},{"key":"25091_CR48","doi-asserted-by":"publisher","first-page":"e0136420","DOI":"10.1371\/journal.pone.0136420","volume":"10","author":"CY Wu","year":"2015","unstructured":"Wu, C. Y. et al. Inactivated Enterovirus 71 Vaccine Produced by 200-L Scale Serum-Free Microcarrier Bioreactor System Provides Cross-Protective Efficacy in Human SCARB2 Transgenic Mouse. PLoS One 10, e0136420, https:\/\/doi.org\/10.1371\/journal.pone.0136420 (2015).","journal-title":"PLoS One"},{"key":"25091_CR49","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1099\/vir.0.83676-0","volume":"89","author":"BH Chua","year":"2008","unstructured":"Chua, B. H. et al. The molecular basis of mouse adaptation by human enterovirus 71. J Gen Virol 89, 1622\u20131632 (2008).","journal-title":"J Gen Virol"},{"key":"25091_CR50","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.virol.2016.11.009","volume":"501","author":"CW Tan","year":"2017","unstructured":"Tan, C. W. et al. VP1 residues around the five-fold axis of enterovirus A71 mediate heparan sulfate interaction. Virology 501, 79\u201387 (2017).","journal-title":"Virology"},{"key":"25091_CR51","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/S0168-1702(00)00235-5","volume":"73","author":"SC Wu","year":"2001","unstructured":"Wu, S. C. & Lee, S. C. Complete nucleotide sequence and cell-line multiplication pattern of the attenuated variant CH2195LA of Japanese encephalitis virus. Virus Res 73, 91\u2013102 (2001).","journal-title":"Virus Res"},{"key":"25091_CR52","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-14-243","volume":"14","author":"B Zhang","year":"2014","unstructured":"Zhang, B. et al. The variations of VP1 protein might be associated with nervous system symptoms caused by enterovirus 71 infection. BMC infectious diseases 14, 243, https:\/\/doi.org\/10.1186\/1471-2334-14-243 (2014).","journal-title":"BMC infectious diseases"},{"key":"25091_CR53","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1007\/s13238-014-0087-3","volume":"5","author":"M Dang","year":"2014","unstructured":"Dang, M. et al. Molecular mechanism of SCARB2-mediated attachment and uncoating of EV71. Protein & cell 5, 692\u2013703, https:\/\/doi.org\/10.1007\/s13238-014-0087-3 (2014).","journal-title":"Protein & cell"},{"key":"25091_CR54","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1097\/INF.0b013e318228ba24","volume":"30","author":"CY Tong","year":"2011","unstructured":"Tong, C. Y., Bible, J. M. & Platt, C. A fatal case of enterovirus 71 infection with a single nucleotide variation in domain V of the 5\u2032 untranslated region. Pediatr Infect Dis J 30, 1013\u20131014, https:\/\/doi.org\/10.1097\/INF.0b013e318228ba24 (2011).","journal-title":"Pediatr Infect Dis J"},{"key":"25091_CR55","doi-asserted-by":"publisher","DOI":"10.1038\/srep20839","volume":"6","author":"Z Li","year":"2016","unstructured":"Li, Z. et al. Identification of a nucleotide in 5\u2032 untranslated region contributing to virus replication and virulence of Coxsackievirus A16. Scientific reports 6, 20839, https:\/\/doi.org\/10.1038\/srep20839 (2016).","journal-title":"Scientific reports"},{"key":"25091_CR56","doi-asserted-by":"publisher","first-page":"e1005033","DOI":"10.1371\/journal.ppat.1005033","volume":"11","author":"C Kataoka","year":"2015","unstructured":"Kataoka, C. et al. The Role of VP1 Amino Acid Residue 145 of Enterovirus 71 in Viral Fitness and Pathogenesis in a Cynomolgus Monkey Model. PLoS pathogens 11, e1005033, https:\/\/doi.org\/10.1371\/journal.ppat.1005033 (2015).","journal-title":"PLoS pathogens"},{"key":"25091_CR57","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1111\/j.1651-2227.2002.tb03292.x","volume":"91","author":"TY Lin","year":"2002","unstructured":"Lin, T. Y. et al. Different proinflammatory reactions in fatal and non-fatal enterovirus 71 infections: implications for early recognition and therapy. Acta Paediatr 91, 632\u2013635 (2002).","journal-title":"Acta Paediatr"},{"key":"25091_CR58","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/S0378-4274(98)00324-5","volume":"102\u2013103","author":"M Aschner","year":"1998","unstructured":"Aschner, M. Immune and inflammatory responses in the CNS: modulation by astrocytes. Toxicology letters 102\u2013103, 283\u2013287 (1998).","journal-title":"Toxicology letters"},{"key":"25091_CR59","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.02.002","author":"R Tinoco","year":"2017","unstructured":"Tinoco, R., Otero, D. C., Takahashi, A. A. & Bradley, L. M. PSGL-1: A New Player in the Immune Checkpoint Landscape. Trends in immunology. https:\/\/doi.org\/10.1016\/j.it.2017.02.002 (2017).","journal-title":"Trends in immunology"},{"key":"25091_CR60","doi-asserted-by":"crossref","unstructured":"Liu, J. et al. Transgenic expression of human P-selectin glycoprotein ligand-1 is not sufficient for enterovirus 71 infection in mice. Arch Virol (2012).","DOI":"10.1007\/s00705-011-1198-2"}],"updated-by":[{"DOI":"10.1038\/s41598-018-26833-3","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2018,6,4]],"date-time":"2018-06-04T00:00:00Z","timestamp":1528070400000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-25091-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-25091-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-25091-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T04:52:09Z","timestamp":1671598329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-25091-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,27]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["25091"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-25091-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,27]]},"assertion":[{"value":"12 June 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 June 2018","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"6688"}}