Characteristics of CVA16 B1c strains isolated for the first time in the Heilongjiang Province of China

Hand, foot, and mouth disease (HFMD) represents a globally prevalent infectious disease that is caused by enteroviruses. Enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16), and coxsackievirus A6 (CVA6) are recognized as the predominant causative agents of HFMD. CVA16 is a member of the genus Enter...

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Main Authors: Tingting Yang, Qiang Sun, Hui Liu, Ming Yang, Shuhong Chen, Wei Sun, Jun Xu, Dongmei Yan, Shuangli Zhu, Zhenzhi Han, Jinbo Xiao, Huanhuan Lu, Ying Liu, Qian Yang, Yong Zhang
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Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2025.1634547/full
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author Tingting Yang
Qiang Sun
Qiang Sun
Qiang Sun
Hui Liu
Ming Yang
Shuhong Chen
Wei Sun
Jun Xu
Dongmei Yan
Dongmei Yan
Dongmei Yan
Shuangli Zhu
Shuangli Zhu
Shuangli Zhu
Zhenzhi Han
Jinbo Xiao
Jinbo Xiao
Jinbo Xiao
Huanhuan Lu
Huanhuan Lu
Huanhuan Lu
Ying Liu
Ying Liu
Ying Liu
Qian Yang
Qian Yang
Qian Yang
Yong Zhang
Yong Zhang
Yong Zhang
author_facet Tingting Yang
Qiang Sun
Qiang Sun
Qiang Sun
Hui Liu
Ming Yang
Shuhong Chen
Wei Sun
Jun Xu
Dongmei Yan
Dongmei Yan
Dongmei Yan
Shuangli Zhu
Shuangli Zhu
Shuangli Zhu
Zhenzhi Han
Jinbo Xiao
Jinbo Xiao
Jinbo Xiao
Huanhuan Lu
Huanhuan Lu
Huanhuan Lu
Ying Liu
Ying Liu
Ying Liu
Qian Yang
Qian Yang
Qian Yang
Yong Zhang
Yong Zhang
Yong Zhang
author_sort Tingting Yang
collection DOAJ
description Hand, foot, and mouth disease (HFMD) represents a globally prevalent infectious disease that is caused by enteroviruses. Enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16), and coxsackievirus A6 (CVA6) are recognized as the predominant causative agents of HFMD. CVA16 is a member of the genus Enterovirus within the family Picornaviridae. B1a and B1b are the most prevalent subgenotypes, whereas the B1c subgenotype is relatively scarce. In this study, a comprehensive analysis was conducted on 15 of CVA16 B1c strains isolated from samples of patients diagnosed with HFMD in Jixi (Heilongjiang Province, China) in 2022. Subsequently, whole genome sequencing of these strains was carried out. Phylogenetic origin and potential recombination events were analyzed by aligning sequences of isolated of CVA16 B1c strains with related sequences deposited in GenBank. The CVA16 B1c isolates examined in this study exhibited a high degree of similarities. Specifically, the nucleotide similarity within the VP1 region ranged from 99.6 to 100%. The average nucleotide substitution rate of CVA16 B1c viruses worldwide was estimated to be 5.14 × 10−3 (4.13–6.27 × 10−3) substitution/site/year, and the most recent common ancestor could be traced back to 2003. The earliest CVA16 B1c strain isolated in China was traced back to 2011. Transmission pathway analysis suggested that Chinese strains may have originated in India. Recombination analysis showed that CVA16 B1c strains likely undergone recombination events with EV-A71 and CVA4. In conclusion, the analysis of a cluster of CVA16 B1c cases detected for the first time in Heilongjiang Province not only expanded the gene sequence library of CVA16 B1c strains in China but also offered an epidemiological basis for further investigations into the antigen–antibody interactions and pathogenicity of CVA16 B1c.
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spelling doaj-art-cc57e64cdd93432a8d891c4e22cfbe522025-08-20T03:44:35ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-08-011610.3389/fmicb.2025.16345471634547Characteristics of CVA16 B1c strains isolated for the first time in the Heilongjiang Province of ChinaTingting Yang0Qiang Sun1Qiang Sun2Qiang Sun3Hui Liu4Ming Yang5Shuhong Chen6Wei Sun7Jun Xu8Dongmei Yan9Dongmei Yan10Dongmei Yan11Shuangli Zhu12Shuangli Zhu13Shuangli Zhu14Zhenzhi Han15Jinbo Xiao16Jinbo Xiao17Jinbo Xiao18Huanhuan Lu19Huanhuan Lu20Huanhuan Lu21Ying Liu22Ying Liu23Ying Liu24Qian Yang25Qian Yang26Qian Yang27Yong Zhang28Yong Zhang29Yong Zhang30Jinan Center for Disease Control and Prevention, Jinan, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Polio Laboratory, World Health Organization Polio Reference Laboratory for the Western Pacific Region, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Health Commission Key Laboratory of Laboratory Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaJinan Center for Disease Control and Prevention, Jinan, ChinaHeilongjiang Provincial Center for Disease Control and Prevention, Harbin, ChinaHeilongjiang Provincial Center for Disease Control and Prevention, Harbin, ChinaHeilongjiang Provincial Center for Disease Control and Prevention, Harbin, ChinaHeilongjiang Provincial Center for Disease Control and Prevention, Harbin, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Polio Laboratory, World Health Organization Polio Reference Laboratory for the Western Pacific Region, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Health Commission Key Laboratory of Laboratory Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Polio Laboratory, World Health Organization Polio Reference Laboratory for the Western Pacific Region, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Health Commission Key Laboratory of Laboratory Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaLaboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Polio Laboratory, World Health Organization Polio Reference Laboratory for the Western Pacific Region, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Health Commission Key Laboratory of Laboratory Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Polio Laboratory, World Health Organization Polio Reference Laboratory for the Western Pacific Region, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Health Commission Key Laboratory of Laboratory Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Polio Laboratory, World Health Organization Polio Reference Laboratory for the Western Pacific Region, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Health Commission Key Laboratory of Laboratory Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Polio Laboratory, World Health Organization Polio Reference Laboratory for the Western Pacific Region, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Health Commission Key Laboratory of Laboratory Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Polio Laboratory, World Health Organization Polio Reference Laboratory for the Western Pacific Region, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Health Commission Key Laboratory of Laboratory Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaHand, foot, and mouth disease (HFMD) represents a globally prevalent infectious disease that is caused by enteroviruses. Enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16), and coxsackievirus A6 (CVA6) are recognized as the predominant causative agents of HFMD. CVA16 is a member of the genus Enterovirus within the family Picornaviridae. B1a and B1b are the most prevalent subgenotypes, whereas the B1c subgenotype is relatively scarce. In this study, a comprehensive analysis was conducted on 15 of CVA16 B1c strains isolated from samples of patients diagnosed with HFMD in Jixi (Heilongjiang Province, China) in 2022. Subsequently, whole genome sequencing of these strains was carried out. Phylogenetic origin and potential recombination events were analyzed by aligning sequences of isolated of CVA16 B1c strains with related sequences deposited in GenBank. The CVA16 B1c isolates examined in this study exhibited a high degree of similarities. Specifically, the nucleotide similarity within the VP1 region ranged from 99.6 to 100%. The average nucleotide substitution rate of CVA16 B1c viruses worldwide was estimated to be 5.14 × 10−3 (4.13–6.27 × 10−3) substitution/site/year, and the most recent common ancestor could be traced back to 2003. The earliest CVA16 B1c strain isolated in China was traced back to 2011. Transmission pathway analysis suggested that Chinese strains may have originated in India. Recombination analysis showed that CVA16 B1c strains likely undergone recombination events with EV-A71 and CVA4. In conclusion, the analysis of a cluster of CVA16 B1c cases detected for the first time in Heilongjiang Province not only expanded the gene sequence library of CVA16 B1c strains in China but also offered an epidemiological basis for further investigations into the antigen–antibody interactions and pathogenicity of CVA16 B1c.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1634547/fullCVA16 B1cepidemiologyevolutionary origin analysisrecombinationenteroviruses
spellingShingle Tingting Yang
Qiang Sun
Qiang Sun
Qiang Sun
Hui Liu
Ming Yang
Shuhong Chen
Wei Sun
Jun Xu
Dongmei Yan
Dongmei Yan
Dongmei Yan
Shuangli Zhu
Shuangli Zhu
Shuangli Zhu
Zhenzhi Han
Jinbo Xiao
Jinbo Xiao
Jinbo Xiao
Huanhuan Lu
Huanhuan Lu
Huanhuan Lu
Ying Liu
Ying Liu
Ying Liu
Qian Yang
Qian Yang
Qian Yang
Yong Zhang
Yong Zhang
Yong Zhang
Characteristics of CVA16 B1c strains isolated for the first time in the Heilongjiang Province of China
Frontiers in Microbiology
CVA16 B1c
epidemiology
evolutionary origin analysis
recombination
enteroviruses
title Characteristics of CVA16 B1c strains isolated for the first time in the Heilongjiang Province of China
title_full Characteristics of CVA16 B1c strains isolated for the first time in the Heilongjiang Province of China
title_fullStr Characteristics of CVA16 B1c strains isolated for the first time in the Heilongjiang Province of China
title_full_unstemmed Characteristics of CVA16 B1c strains isolated for the first time in the Heilongjiang Province of China
title_short Characteristics of CVA16 B1c strains isolated for the first time in the Heilongjiang Province of China
title_sort characteristics of cva16 b1c strains isolated for the first time in the heilongjiang province of china
topic CVA16 B1c
epidemiology
evolutionary origin analysis
recombination
enteroviruses
url https://www.frontiersin.org/articles/10.3389/fmicb.2025.1634547/full
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