PMID- 34834966
OWN - NLM
STAT- MEDLINE
DCOM- 20220214
LR  - 20220214
IS  - 1999-4915 (Electronic)
IS  - 1999-4915 (Linking)
VI  - 13
IP  - 11
DP  - 2021 Oct 26
TI  - The Stem-Loop I of Senecavirus A IRES Is Essential for Cap-Independent 
      Translation Activity and Virus Recovery.
LID - 10.3390/v13112159 [doi]
LID - 2159
AB  - Senecavirus A (SVA) is a picornavirus that causes vesicular disease in swine and 
      the only member of the Senecavirus genus. Like in all members of Picornaviridae, 
      the 5' untranslated region (5'UTR) of SVA contains an internal ribosome entry 
      site (IRES) that initiates cap-independent translation. For example, the 
      replacement of the IRES of foot-and-mouth disease virus (FMDV) with its relative 
      bovine rhinitis B virus (BRBV) affects the viral translation efficiency and 
      virulence. Structurally, the IRES from SVA resembles that of hepatitis C virus 
      (HCV), a flavivirus. Given the roles of the IRES in cap-independent translation 
      for picornaviruses, we sought to functionally characterize the IRES of this genus 
      by studying chimeric viruses generated by exchanging the native SVA IRES with 
      that of HCV either entirely or individual domains. First, the results showed that 
      a chimeric SVA virus harboring the IRES from HCV, H-SVA, is viable and replicated 
      normally in rodent-derived BHK-21 cells but displays replication defects in 
      porcine-derived ST cells. In the generation of chimeric viruses in which 
      domain-specific elements from SVA were replaced with those of HCV, we identified 
      an essential role for the stem-loop I element for IRES activity and recombinant 
      virus recovery. Furthermore, a series of stem-loop I mutants allowed us to 
      functionally characterize discrete IRES regions and correlate impaired IRES 
      activities, using reporter systems with our inability to recover recombinant 
      viruses in two different cell types. Interestingly, mutant viruses harboring 
      partially defective IRES were viable. However, no discernable replication 
      differences were observed, relative to the wild-type virus, suggesting the 
      cooperation of additional factors, such as intermolecular viral RNA interactions, 
      act in concert in regulating IRES-dependent translation during infection. 
      Altogether, we found that the stem-loop I of SVA is an essential element for 
      IRES-dependent translation activity and viral replication.
FAU - Wang, Nana
AU  - Wang N
AD  - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research 
      Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.
FAU - Wang, Haiwei
AU  - Wang H
AD  - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research 
      Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.
FAU - Shi, Jiabao
AU  - Shi J
AD  - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research 
      Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.
FAU - Li, Chen
AU  - Li C
AD  - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research 
      Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.
FAU - Liu, Xinran
AU  - Liu X
AD  - Department of Chemistry, The Pennsylvania State University, University Park, PA 
      16802, USA.
FAU - Fan, Junhao
AU  - Fan J
AD  - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research 
      Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.
FAU - Sun, Chao
AU  - Sun C
AD  - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research 
      Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.
FAU - Cameron, Craig E
AU  - Cameron CE
AD  - Department of Microbiology and Immunology, University of North Carolina School of 
      Medicine, Chapel Hill, NC 27516, USA.
FAU - Qi, Hong
AU  - Qi H
AD  - Key Laboratory of Urban Water Resource and Environment, Harbin Institute of 
      Technology, School of Environment, Harbin 150090, China.
FAU - Yu, Li
AU  - Yu L
AD  - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research 
      Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211026
PL  - Switzerland
TA  - Viruses
JT  - Viruses
JID - 101509722
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Internal Ribosome Entry Sites)
RN  - 0 (RNA, Viral)
RN  - Senecavirus A
SB  - IM
MH  - 5' Untranslated Regions
MH  - Animals
MH  - Cell Line
MH  - DNA Viruses/genetics
MH  - Foot-and-Mouth Disease Virus/genetics
MH  - Gene Expression Regulation, Viral
MH  - Hepacivirus/genetics
MH  - *Internal Ribosome Entry Sites
MH  - Mutagenesis, Site-Directed
MH  - Picornaviridae/*genetics/*physiology
MH  - Picornaviridae Infections/virology
MH  - RNA, Viral/genetics
MH  - *Virus Replication/genetics
PMC - PMC8619302
OTO - NOTNLM
OT  - IRES
OT  - Senecavirus A
OT  - picornavirus
OT  - stem-loop I
OT  - translation
OT  - viral replication
COIS- The authors declare that they have no competing interest.
EDAT- 2021/11/28 06:00
MHDA- 2022/02/15 06:00
PMCR- 2021/10/26
CRDT- 2021/11/27 01:26
PHST- 2021/09/26 00:00 [received]
PHST- 2021/10/07 00:00 [revised]
PHST- 2021/10/22 00:00 [accepted]
PHST- 2021/11/27 01:26 [entrez]
PHST- 2021/11/28 06:00 [pubmed]
PHST- 2022/02/15 06:00 [medline]
PHST- 2021/10/26 00:00 [pmc-release]
AID - v13112159 [pii]
AID - viruses-13-02159 [pii]
AID - 10.3390/v13112159 [doi]
PST - epublish
SO  - Viruses. 2021 Oct 26;13(11):2159. doi: 10.3390/v13112159.