title: Identification of a nucleotide in 5' untranslated region contributing to virus replication and virulence of Coxsackievirus A16.
abstract: Coxsackievirus A16 (CA16) and enterovirus 71 (EV71) are two main causative pathogens of hand, foot and mouth disease (HFMD). Unlike EV71, virulence determinants of CA16, particularly within 5' untranslated region (5'UTR), have not been investigated until now. Here, a series of nucleotides present in 5'UTR of lethal but not in non-lethal CA16 strains were screened by aligning nucleotide sequences of lethal circulating Changchun CA16 and the prototype G10 as well as non-lethal SHZH05 strains. A representative infectious clone based on a lethal Changchun024 sequence and infectious mutants with various nucleotide alterations in 5'UTR were constructed and further investigated by assessing virus replication in vitro and virulence in neonatal mice. Compared to the lethal infectious clone, the M2 mutant with a change from cytosine to uracil at nucleotide 104 showed weaker virulence and lower replication capacity. The predicted secondary structure of the 5'UTR of CA16 RNA showed that M2 mutant located between the cloverleaf and stem-loop II, affected interactions between the 5'UTR and the heterogeneous nuclear ribonucleoprotein K (hnRNP K) and A1 (hnRNP A1) that are important for translational activity. Thus, our research determined a virulence-associated site in the 5'UTR of CA16, providing a crucial molecular target for antiviral drug development.
authors: First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province, China.|College of Life Science, Jilin University, Changchun, Jilin Province, China.
authors: Zhaolong
authors: Z
authors: Li
authors: First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province, China.
authors: Xin
authors: X
authors: Liu
authors: First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province, China.
authors: Shaohua
authors: S
authors: Wang
authors: First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province, China.
authors: Jingliang
authors: J
authors: Li
authors: First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province, China.
authors: Min
authors: M
authors: Hou
authors: First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province, China.|College of Life Science, Jilin University, Changchun, Jilin Province, China.
authors: Guanchen
authors: G
authors: Liu
authors: First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province, China.
authors: Wenyan
authors: W
authors: Zhang
authors: First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province, China.
authors: Xiao-Fang
authors: XF
authors: Yu
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D003384:Coxsackievirus Infections / Q000401:mortality / Q000821:virology*; D004195:Disease Models, Animal; D004770:Enterovirus / Q000235:genetics* / Q000472:pathogenicity*; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000378:metabolism; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000378:metabolism; D051379:Mice; D009017:Morbidity; D009026:Mortality; D009154:Mutation; D009690:Nucleic Acid Conformation; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D017422:Sequence Analysis, DNA; D014774:Virulence / Q000235:genetics; D014779:Virus Replication
chemical_list: D020121:5' Untranslated Regions; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D012367:RNA, Viral