{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:56:32Z","timestamp":1787061392269,"version":"build-2736575974"},"reference-count":85,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health Research Institutes","award":["IV-102-PP-10"],"award-info":[{"award-number":["IV-102-PP-10"]}]},{"name":"National Health Research Institutes","award":["IV-111-PP-06"],"award-info":[{"award-number":["IV-111-PP-06"]}]},{"name":"National Health Research Institutes","award":["HP110073-7"],"award-info":[{"award-number":["HP110073-7"]}]},{"name":"National Health Research Institutes","award":["110-2320-B-006-031-MY3"],"award-info":[{"award-number":["110-2320-B-006-031-MY3"]}]},{"name":"Taiwan Centers of Disease Control, Ministry of Health and Welfare","award":["IV-102-PP-10"],"award-info":[{"award-number":["IV-102-PP-10"]}]},{"name":"Taiwan Centers of Disease Control, Ministry of Health and Welfare","award":["IV-111-PP-06"],"award-info":[{"award-number":["IV-111-PP-06"]}]},{"name":"Taiwan Centers of Disease Control, Ministry of Health and Welfare","award":["HP110073-7"],"award-info":[{"award-number":["HP110073-7"]}]},{"name":"Taiwan Centers of Disease Control, Ministry of Health and Welfare","award":["110-2320-B-006-031-MY3"],"award-info":[{"award-number":["110-2320-B-006-031-MY3"]}]},{"name":"National Science and Technology Council","award":["IV-102-PP-10"],"award-info":[{"award-number":["IV-102-PP-10"]}]},{"name":"National Science and Technology Council","award":["IV-111-PP-06"],"award-info":[{"award-number":["IV-111-PP-06"]}]},{"name":"National Science and Technology Council","award":["HP110073-7"],"award-info":[{"award-number":["HP110073-7"]}]},{"name":"National Science and Technology Council","award":["110-2320-B-006-031-MY3"],"award-info":[{"award-number":["110-2320-B-006-031-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Coxsackievirus A16 (CVA16) is well known for causing hand-foot-and-mouth disease (HFMD) and outbreaks were frequently reported in Taiwan in the past twenty years. The epidemiology and genetic variations of CVA16 in Taiwan from 1998 to 2021 were analyzed in this study. CVA16 infections usually occurred in early summer and early winter, and showed increased incidence in 1998, 2000\u20132003, 2005, 2007\u20132008, and 2010 in Taiwan. Little or no CVA16 was detected from 2017 to 2021. CVA16 infection was prevalent in patients between 1 to 3 years old. A total of 69 isolates were sequenced. Phylogenetic analysis based on the VP1 region showed that CVA16 subgenotype B1 was dominantly isolated in Taiwan from 1998 to 2019, and B2 was identified only from isolates collected in 1999 and 2000. There was a high frequency of synonymous mutations in the amino acid sequences of the VP1 region among CVA16 isolates, with the exception of position 145 which showed positive selection. The recombination analysis of the whole genome of CVA16 isolates indicated that the 5\u2032-untranslated region and the non-structural protein region of CVA16 subgenotype B1 were recombined with Coxsackievirus A4 (CVA4) and enterovirus A71 (EVA71) genotype A, respectively. The recombination pattern of subgenotype B2 was similar to B1, however, the 3D region was similar to EVA71 genotype B. Cross-neutralization among CVA16 showed that mouse antisera from various subgenotypes viruses can cross-neutralize different genotype with high neutralizing antibody titers. These results suggest that the dominant CVA16 genotype B1 can serve as a vaccine candidate for CVA16.<\/jats:p>","DOI":"10.3390\/v14102306","type":"journal-article","created":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:34:30Z","timestamp":1666312470000},"page":"2306","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genetic and Cross Neutralization Analyses of Coxsackievirus A16 Circulating in Taiwan from 1998 to 2021 Suggest Dominant Genotype B1 can Serve as Vaccine Candidate"],"prefix":"10.3390","volume":"14","author":[{"given":"Dayna","family":"Cheng","sequence":"first","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yo-Wei","family":"Chiu","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9127-7616","authenticated-orcid":false,"given":"Sheng-Wen","family":"Huang","sequence":"additional","affiliation":[{"name":"National Mosquito-Borne Diseases Control Research Center, National Health Research Institutes, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Yin","family":"Lien","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Lun","family":"Chang","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huey-Pin","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan 70101, Taiwan"},{"name":"National Mosquito-Borne Diseases Control Research Center, National Health Research Institutes, Tainan 70101, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4127-4046","authenticated-orcid":false,"given":"Jen-Ren","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan 70101, Taiwan"},{"name":"Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"veaa084","DOI":"10.1093\/ve\/veaa084","article-title":"Genomic epidemiology of coxsackievirus A16 in mainland of China, 2000\u201318","volume":"6","author":"Han","year":"2020","journal-title":"Virus Evol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8273","DOI":"10.1016\/j.vaccine.2020.11.031","article-title":"Coxsackieviruses A6 and A16 associated with hand, foot, and mouth disease in Vietnam, 2008\u20132017: Essential information for rational vaccine design","volume":"38","author":"Dao","year":"2020","journal-title":"Vaccine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1093\/jpids\/piaa111","article-title":"A Different Epidemiology of Enterovirus A and Enterovirus B Co-circulating in Korea, 2012\u20132019","volume":"10","author":"Kang","year":"2021","journal-title":"J. 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