title: Phenotypic and genomic characterization of human coxsackievirus A16 strains with distinct virulence in mice.
abstract: Human coxsackievirus A16 (CA16) infection results in hand, foot, and mouth disease (HFMD) along with other severe neurological diseases in children and poses an important public health threat in Asian countries. During an HFMD epidemic in 2009 in Guangdong, China, two CA16 strains (GD09/119 and GD09/24) were isolated and characterized. Although both strains were similar in plaque morphology and growth properties in vitro, the two isolates exhibited distinct pathogenicity in neonatal mice upon intraperitoneal or intracranial injection. Complete genome sequences of both CA16 strains were determined, and the possible virulence determinants were analyzed and predicted. Phylogenetic analysis revealed that these CA16 isolates from Guangdong belonged to the B1b genotype and were closely related to other recent CA16 strains isolated in mainland China. Similarity and bootscanning analyses of these CA16 strains detected homologous recombination with the EV71 prototype strain BrCr in the non-structural gene regions and the 3'-untranslated regions. Together, the phenotypic and genomic characterizations of the two clinical CA16 isolates circulating in China were compared in detail, and the potential amino acid residues responsible for CA16 virulence in mice were predicted. These findings will help explain the evolutionary relationship of the CA16 strains circulating in China, warranting future studies investigating enterovirus virulence.
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Han
authors.affiliation: Laboratory of Emerging Infectious Disease and Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, No. 253 Gong ye da dao zhong, Guangzhou, Guangdong 510282, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yu
authors.affiliation: Laboratory of Emerging Infectious Disease and Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, No. 253 Gong ye da dao zhong, Guangzhou, Guangdong 510282, China.
authors.forename: Yu-Xian
authors.initials: YX
authors.lastname: Pan
authors.affiliation: Laboratory of Emerging Infectious Disease and Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, No. 253 Gong ye da dao zhong, Guangzhou, Guangdong 510282, China.
authors.forename: Si-Jie
authors.initials: SJ
authors.lastname: He
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Xu
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Rui-Yuan
authors.initials: RY
authors.lastname: Cao
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Yue-Xiang
authors.initials: YX
authors.lastname: Li
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Shun-Ya
authors.initials: SY
authors.lastname: Zhu
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: E-De
authors.initials: ED
authors.lastname: Qin
authors.affiliation: Laboratory of Emerging Infectious Disease and Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, No. 253 Gong ye da dao zhong, Guangzhou, Guangdong 510282, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Che
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China. Electronic address: qincf@bmi.ac.cn.
authors.forename: Cheng-Feng
authors.initials: CF
authors.lastname: Qin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D029821:Enterovirus A, Human / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D005260:Female; D016679:Genome, Viral; D023281:Genomics; D006232:Hand, Foot and Mouth Disease / Q000821:virology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010641:Phenotype; D010802:Phylogeny; D016415:Sequence Alignment; D014774:Virulence
keywords: Homologous recombination; Human coxsackievirus A16; Phylogenetics; Virulence