PMID- 26861413
OWN - NLM
STAT- MEDLINE
DCOM- 20170106
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Feb 10
TI  - Identification of a nucleotide in 5' untranslated region contributing to virus 
      replication and virulence of Coxsackievirus A16.
PG  - 20839
LID - 10.1038/srep20839 [doi]
LID - 20839
AB  - 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.
FAU - Li, Zhaolong
AU  - Li Z
AD  - First Hospital of Jilin University, Institute of Virology and AIDS Research, 
      Changchun, Jilin Province, China.
AD  - College of Life Science, Jilin University, Changchun, Jilin Province, China.
FAU - Liu, Xin
AU  - Liu X
AD  - First Hospital of Jilin University, Institute of Virology and AIDS Research, 
      Changchun, Jilin Province, China.
FAU - Wang, Shaohua
AU  - Wang S
AD  - First Hospital of Jilin University, Institute of Virology and AIDS Research, 
      Changchun, Jilin Province, China.
FAU - Li, Jingliang
AU  - Li J
AD  - First Hospital of Jilin University, Institute of Virology and AIDS Research, 
      Changchun, Jilin Province, China.
FAU - Hou, Min
AU  - Hou M
AD  - First Hospital of Jilin University, Institute of Virology and AIDS Research, 
      Changchun, Jilin Province, China.
FAU - Liu, Guanchen
AU  - Liu G
AD  - First Hospital of Jilin University, Institute of Virology and AIDS Research, 
      Changchun, Jilin Province, China.
AD  - College of Life Science, Jilin University, Changchun, Jilin Province, China.
FAU - Zhang, Wenyan
AU  - Zhang W
AD  - First Hospital of Jilin University, Institute of Virology and AIDS Research, 
      Changchun, Jilin Province, China.
FAU - Yu, Xiao-Fang
AU  - Yu XF
AD  - First Hospital of Jilin University, Institute of Virology and AIDS Research, 
      Changchun, Jilin Province, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160210
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Heterogeneous Nuclear Ribonucleoprotein A1)
RN  - 0 (Heterogeneous-Nuclear Ribonucleoprotein Group A-B)
RN  - 0 (Heterogeneous-Nuclear Ribonucleoprotein K)
RN  - 0 (RNA, Viral)
SB  - IM
MH  - *5' Untranslated Regions
MH  - Animals
MH  - Animals, Newborn
MH  - Base Sequence
MH  - Coxsackievirus Infections/mortality/*virology
MH  - Disease Models, Animal
MH  - Enterovirus/*genetics/*pathogenicity
MH  - Heterogeneous Nuclear Ribonucleoprotein A1
MH  - Heterogeneous-Nuclear Ribonucleoprotein Group A-B/metabolism
MH  - Heterogeneous-Nuclear Ribonucleoprotein K/metabolism
MH  - Mice
MH  - Morbidity
MH  - Mortality
MH  - Mutation
MH  - Nucleic Acid Conformation
MH  - RNA, Viral/chemistry/genetics
MH  - Sequence Analysis, DNA
MH  - Virulence/genetics
MH  - *Virus Replication
PMC - PMC4748407
EDAT- 2016/02/11 06:00
MHDA- 2017/01/07 06:00
PMCR- 2016/02/10
CRDT- 2016/02/11 06:00
PHST- 2015/10/20 00:00 [received]
PHST- 2016/01/13 00:00 [accepted]
PHST- 2016/02/11 06:00 [entrez]
PHST- 2016/02/11 06:00 [pubmed]
PHST- 2017/01/07 06:00 [medline]
PHST- 2016/02/10 00:00 [pmc-release]
AID - srep20839 [pii]
AID - 10.1038/srep20839 [doi]
PST - epublish
SO  - Sci Rep. 2016 Feb 10;6:20839. doi: 10.1038/srep20839.