{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:34:05Z","timestamp":1791236045222,"version":"4.1.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virol J"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hand, foot and mouth disease (HFMD), a common contagious disease that usually affects children, is normally mild but can have life-threatening manifestations. It can be caused by enteroviruses, particularly Coxsackieviruses and human enterovirus 71 (HEV71) with highly variable clinical manifestations. In the spring of 2008, a large, unprecedented HFMD outbreak in Fuyang city of Anhui province in the central part of southeastern China resulted in a high aggregation of fatal cases. In this study, epidemiologic and clinical investigations, laboratory testing, and genetic analyses were performed to identify the causal pathogen of the outbreak. Of the 6,049 cases reported between 1 March and 9 May of 2008, 3023 (50%) were hospitalized, 353 (5.8%) were severe and 22 (0.36%) were fatal. HEV71 was confirmed as the etiological pathogen of the outbreak. Phylogenetic analyses of entire VP1 capsid protein sequence of 45 Fuyang HEV71 isolates showed that they belong to C4a cluster of the C4 subgenotype. In addition, genetic recombinations were found in the 3D region (RNA-dependent RNA polymerase, a major component of the viral replication complex of the genome) between the Fuyang HEV71 strain and Coxsackievirus A16 (CV-A16), resulting in a recombination virus. In conclusion, an emerging recombinant HEV71 was responsible for the HFMD outbreak in Fuyang City of China, 2008.<\/jats:p>","DOI":"10.1186\/1743-422x-7-94","type":"journal-article","created":{"date-parts":[[2010,5,12]],"date-time":"2010-05-12T02:14:19Z","timestamp":1273630459000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":426,"title":["An emerging recombinant human enterovirus 71 responsible for the 2008 outbreak of Hand Foot and Mouth Disease in Fuyang city of China"],"prefix":"10.1186","volume":"7","author":[{"given":"Yan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weizhong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naiying","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songtao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangli","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aili","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueping","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfeng","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijian","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junling","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiwen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dexin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,5,12]]},"reference":[{"key":"839_CR1","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1093\/infdis\/129.6.637","volume":"129","author":"RC Schmidt","year":"1974","unstructured":"Schmidt RC, Maassab HF: Local immunity to influenza virus in chicken tracheal organ cultures. J Infect Dis 1974, 129: 637-643.","journal-title":"J Infect Dis"},{"key":"839_CR2","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1056\/NEJM199909233411301","volume":"341","author":"M Ho","year":"1999","unstructured":"Ho M, Chen ER, Hsu KH, Twu SJ, Chen KT, Tsai SF, Wang JR, Shih SR: An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group. N Engl J Med 1999, 341: 929-935. 10.1056\/NEJM199909233411301","journal-title":"N Engl J Med"},{"key":"839_CR3","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1086\/314032","volume":"31","author":"LG Chan","year":"2000","unstructured":"Chan LG, Parashar UD, Lye MS, Ong FG, Zaki SR, Alexander JP, Ho KK, Han LL, Pallansch MA, Suleiman AB, et al.: Deaths of children during an outbreak of hand, foot, and mouth disease in sarawak, malaysia: clinical and pathological characteristics of the disease. For the Outbreak Study Group. Clin Infect Dis 2000, 31: 678-683. 10.1086\/314032","journal-title":"Clin Infect Dis"},{"key":"839_CR4","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1086\/318454","volume":"32","author":"P McMinn","year":"2001","unstructured":"McMinn P, Stratov I, Nagarajan L, Davis S: Neurological manifestations of enterovirus 71 infection in children during an outbreak of hand, foot, and mouth disease in Western Australia. Clin Infect Dis 2001, 32: 236-242. 10.1086\/318454","journal-title":"Clin Infect Dis"},{"key":"839_CR5","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1128\/JCM.40.1.10-15.2002","volume":"40","author":"JR Wang","year":"2002","unstructured":"Wang JR, Tuan YC, Tsai HP, Yan JJ, Liu CC, Su IJ: Change of major genotype of enterovirus 71 in outbreaks of hand-foot-and-mouth disease in Taiwan between 1998 and 2000. J Clin Microbiol 2002, 40: 10-15. 10.1128\/JCM.40.1.10-15.2002","journal-title":"J Clin Microbiol"},{"key":"839_CR6","doi-asserted-by":"publisher","first-page":"78","DOI":"10.3201\/eid1301.020112","volume":"9","author":"KP Chan","year":"2003","unstructured":"Chan KP, Goh KT, Chong CY, Teo ES, Lau G, Ling AE: Epidemic hand, foot and mouth disease caused by human enterovirus 71, Singapore. Emerg Infect Dis 2003, 9: 78-85.","journal-title":"Emerg Infect Dis"},{"key":"839_CR7","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1046\/j.1442-200x.2004.01868.x","volume":"46","author":"H Shimizu","year":"2004","unstructured":"Shimizu H, Utama A, Onnimala N, Li C, Li-Bi Z, Yu-Jie M, Pongsuwanna Y, Miyamura T: Molecular epidemiology of enterovirus 71 infection in the Western Pacific Region. Pediatr Int 2004, 46: 231-235. 10.1046\/j.1442-200x.2004.01868.x","journal-title":"Pediatr Int"},{"key":"839_CR8","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.jcv.2009.02.002","volume":"44","author":"Y Zhang","year":"2009","unstructured":"Zhang Y, Tan XJ, Wang HY, Yan DM, Zhu SL, Wang DY, Ji F, Wang XJ, Gao YJ, Chen L, et al.: An outbreak of hand, foot, and mouth disease associated with subgenotype C4 of human enterovirus 71 in Shandong, China. J Clin Virol 2009, 44: 262-267. 10.1016\/j.jcv.2009.02.002","journal-title":"J Clin Virol"},{"key":"839_CR9","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1146\/annurev.mi.44.100190.003131","volume":"44","author":"AC Palmenberg","year":"1990","unstructured":"Palmenberg AC: Proteolytic processing of picornaviral polyprotein. Annu Rev Microbiol 1990, 44: 603-623. 10.1146\/annurev.mi.44.100190.003131","journal-title":"Annu Rev Microbiol"},{"key":"839_CR10","doi-asserted-by":"publisher","first-page":"3835","DOI":"10.1128\/JCM.43.8.3835-3839.2005","volume":"43","author":"L Li","year":"2005","unstructured":"Li L, He Y, Yang H, Zhu J, Xu X, Dong J, Zhu Y, Jin Q: Genetic characteristics of human enterovirus 71 and coxsackievirus A16 circulating from 1999 to 2004 in Shenzhen, People's Republic of China. J Clin Microbiol 2005, 43: 3835-3839. 10.1128\/JCM.43.8.3835-3839.2005","journal-title":"J Clin Microbiol"},{"key":"839_CR11","first-page":"648","volume":"43","author":"ZH Yang","year":"2005","unstructured":"Yang ZH, Zhu QR, Li XZ, Wang XH, Wang JS, Hu JY, Tang W, Cui AL: [Detection of enterovirus 71 and coxsackievirus A16 from children with hand, foot and mouth disease in Shanghai, 2002]. Zhonghua Er Ke Za Zhi 2005, 43: 648-652.","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"839_CR12","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/S0168-1702(00)00162-3","volume":"68","author":"SR Shih","year":"2000","unstructured":"Shih SR, Ho MS, Lin KH, Wu SL, Chen YT, Wu CN, Lin TY, Chang LY, Tsao KC, Ning HC, et al.: 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: 127-136. 10.1016\/S0168-1702(00)00162-3","journal-title":"Virus Res"},{"key":"839_CR13","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/S1386-6532(00)00067-6","volume":"17","author":"JJ Yan","year":"2000","unstructured":"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: 13-22. 10.1016\/S1386-6532(00)00067-6","journal-title":"J Clin Virol"},{"key":"839_CR14","unstructured":"Ma H, He F, Wan J, Jin D, Zhu L, Liu X, Liu Q, Zhang G, Ding Z, Fontaine RE, et al.: Glucocorticoid and Pyrazolone Treatment of Acute Fever is a Risk Factor for Critical and Life-Threatening Human Enterovirus 71 Infection During an Outbreak in China, 2008. Pediatr Infect Dis J"},{"key":"839_CR15","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1086\/319255","volume":"183","author":"KD Yang","year":"2001","unstructured":"Yang KD, Yang MY, Li CC, Lin SF, Chong MC, Wang CL, Chen RF, Lin TY: Altered cellular but not humoral reactions in children with complicated enterovirus 71 infections in Taiwan. J Infect Dis 2001, 183: 850-856. 10.1086\/319255","journal-title":"J Infect Dis"},{"key":"839_CR16","doi-asserted-by":"publisher","first-page":"3263","DOI":"10.1099\/vir.0.81195-0","volume":"86","author":"ML Liu","year":"2005","unstructured":"Liu ML, Lee YP, Wang YF, Lei HY, Liu CC, Wang SM, Su IJ, Wang JR, Yeh TM, Chen SH, Yu CK: Type I interferons protect mice against enterovirus 71 infection. J Gen Virol 2005, 86: 3263-3269. 10.1099\/vir.0.81195-0","journal-title":"J Gen Virol"},{"key":"839_CR17","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1203\/01.pdr.0000238247.86041.19","volume":"60","author":"LY Chang","year":"2006","unstructured":"Chang LY, Hsiung CA, Lu CY, Lin TY, Huang FY, Lai YH, Chiang YP, Chiang BL, Lee CY, Huang LM: Status of cellular rather than humoral immunity is correlated with clinical outcome of enterovirus 71. Pediatr Res 2006, 60: 466-471. 10.1203\/01.pdr.0000238247.86041.19","journal-title":"Pediatr Res"},{"key":"839_CR18","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.3201\/eid1008.040059","volume":"10","author":"YF Chan","year":"2004","unstructured":"Chan YF, AbuBaker S: Recombinant human enterovirus 71 in hand, foot and mouth disease patients. Emerg Infect Dis 2004, 10: 1468-1470.","journal-title":"Emerg Infect Dis"},{"key":"839_CR19","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/1471-2180-6-74","volume":"6","author":"C Yoke-Fun","year":"2006","unstructured":"Yoke-Fun C, AbuBakar S: Phylogenetic evidence for inter-typic recombination in the emergence of human enterovirus 71 subgenotypes. BMC Microbiol 2006, 6: 74. 10.1186\/1471-2180-6-74","journal-title":"BMC Microbiol"},{"key":"839_CR20","doi-asserted-by":"crossref","first-page":"8741","DOI":"10.1128\/JVI.73.10.8741-8749.1999","volume":"73","author":"J Santti","year":"1999","unstructured":"Santti J, Hyypia T, Kinnunen L, Salminen M: Evidence of recombination among enteroviruses. J Virol 1999, 73: 8741-8749.","journal-title":"J Virol"},{"key":"839_CR21","doi-asserted-by":"publisher","first-page":"2437","DOI":"10.1099\/0022-1317-83-10-2437","volume":"83","author":"S AbuBakar","year":"2002","unstructured":"AbuBakar S, Wong PF, Chan YF: Emergence of dengue virus type 4 genotype IIA in Malaysia. J Gen Virol 2002, 83: 2437-2442.","journal-title":"J Gen Virol"},{"key":"839_CR22","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, Aoki Y, Suto A, Ootani K, Katsushima N, Itagaki T, Ohmi A, Okamoto M, Nishimura H, Matsuzaki Y, et al.: Cross-antigenicity among EV71 strains from different genogroups isolated in Yamagata, Japan, between 1990 and 2007. Vaccine 2009, 27: 3153-3158. 10.1016\/j.vaccine.2009.03.060","journal-title":"Vaccine"},{"key":"839_CR23","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/0168-1702(92)90124-R","volume":"24","author":"CF Yang","year":"1992","unstructured":"Yang CF, De L, Yang SJ, Ruiz Gomez J, Cruz JR, Holloway BP, Pallansch MA, Kew OM: Genotype-specific in vitro amplification of sequences of the wild type 3 polioviruses from Mexico and Guatemala. Virus Res 1992, 24: 277-296. 10.1016\/0168-1702(92)90124-R","journal-title":"Virus Res"},{"key":"839_CR24","first-page":"95","volume":"41","author":"T Hall","year":"1999","unstructured":"Hall T: Bioedit: a user-friendly biological sequence alignment editor and analysis program forWindows 95\/98\/NT. Nucl Acids Symp 1999, 41: 95-98.","journal-title":"Nucl Acids Symp"},{"key":"839_CR25","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1093\/molbev\/msm092","volume":"24","author":"KDJNM Tamura","year":"2007","unstructured":"Tamura KDJNM, Kumar S: MEGA4: molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 2007, 24: 1596-1599. 10.1093\/molbev\/msm092","journal-title":"Mol Biol Evol"},{"key":"839_CR26","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1089\/aid.1995.11.1423","volume":"11","author":"MO Salminen","year":"1995","unstructured":"Salminen MO, Carr JK, Burke DS, McCutchan FE: Identification of breakpoints in intergenotypic recombinants of HIV type 1 by bootscanning. AIDS Res Hum Retroviruses 1995, 11: 1423-1425. 10.1089\/aid.1995.11.1423","journal-title":"AIDS Res Hum Retroviruses"}],"container-title":["Virology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1743-422X-7-94.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T01:34:06Z","timestamp":1630460046000},"score":1,"resource":{"primary":{"URL":"https:\/\/virologyj.biomedcentral.com\/articles\/10.1186\/1743-422X-7-94"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,5,12]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["839"],"URL":"https:\/\/doi.org\/10.1186\/1743-422x-7-94","relation":{},"ISSN":["1743-422X"],"issn-type":[{"value":"1743-422X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,5,12]]},"assertion":[{"value":"8 March 2010","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2010","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2010","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"94"}}