PMID- 19278709
OWN - NLM
STAT- MEDLINE
DCOM- 20090619
LR  - 20211020
IS  - 1096-0341 (Electronic)
IS  - 0042-6822 (Print)
IS  - 0042-6822 (Linking)
VI  - 387
IP  - 1
DP  - 2009 Apr 25
TI  - The 5'UTR-specific mutation in VEEV TC-83 genome has a strong effect on RNA 
      replication and subgenomic RNA synthesis, but not on translation of the encoded 
      proteins.
PG  - 211-21
LID - 10.1016/j.virol.2009.02.027 [doi]
AB  - Venezuelan equine encephalitis virus (VEEV) is one of the most pathogenic members 
      of the Alphavirus genus in the Togaviridae family. Viruses in the VEEV 
      serocomplex continuously circulate in the Central and South America. The only 
      currently available attenuated strain VEEV TC-83 is being used only for 
      vaccination of at-risk laboratory workers and military personnel. Its attenuated 
      phenotype was shown to rely only on two point mutations, one of which, G3A, was 
      found in the 5' untranslated region (5'UTR) of the viral genome. Our data 
      demonstrate that the G3A mutation strongly affects the secondary structure of 
      VEEV 5'UTR, but has only a minor effect on translation. The indicated mutation 
      increases replication of the viral genome, downregulates transcription of the 
      subgenomic RNA, and, thus, affects the ratio of genomic and subgenomic RNA 
      synthesis. These findings and the previously reported G3A-induced, higher 
      sensitivity of VEEV TC-83 to IFN-alpha/beta suggest a plausible explanation for 
      its attenuated phenotype.
FAU - Kulasegaran-Shylini, Raghavendran
AU  - Kulasegaran-Shylini R
AD  - Department of Biochemistry and Molecular Biology, University of Texas Medical 
      Branch, Galveston, TX 77555-1157, USA.
FAU - Thiviyanathan, Varatharasa
AU  - Thiviyanathan V
FAU - Gorenstein, David G
AU  - Gorenstein DG
FAU - Frolov, Ilya
AU  - Frolov I
LA  - eng
GR  - N01HV28184/HL/NHLBI NIH HHS/United States
GR  - R01 AI070207/AI/NIAID NIH HHS/United States
GR  - R01 AI070207-01A2/AI/NIAID NIH HHS/United States
GR  - AI070207/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090317
PL  - United States
TA  - Virology
JT  - Virology
JID - 0110674
RN  - 0 (5' Untranslated Regions)
RN  - 0 (RNA, Viral)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - 5' Untranslated Regions/*genetics
MH  - Animals
MH  - Cell Line
MH  - Cricetinae
MH  - Encephalitis Virus, Venezuelan Equine/*genetics/metabolism/pathogenicity
MH  - Gene Expression Regulation, Viral
MH  - Genome, Viral/*genetics
MH  - Mice
MH  - NIH 3T3 Cells
MH  - Protein Biosynthesis/*genetics
MH  - RNA, Viral/*biosynthesis/genetics
MH  - Viral Proteins/*metabolism
MH  - Virus Replication
PMC - PMC2675632
MID - NIHMS100420
EDAT- 2009/03/13 09:00
MHDA- 2009/06/20 09:00
PMCR- 2010/04/25
CRDT- 2009/03/13 09:00
PHST- 2008/12/23 00:00 [received]
PHST- 2009/01/20 00:00 [revised]
PHST- 2009/02/18 00:00 [accepted]
PHST- 2009/03/13 09:00 [entrez]
PHST- 2009/03/13 09:00 [pubmed]
PHST- 2009/06/20 09:00 [medline]
PHST- 2010/04/25 00:00 [pmc-release]
AID - S0042-6822(09)00138-X [pii]
AID - 10.1016/j.virol.2009.02.027 [doi]
PST - ppublish
SO  - Virology. 2009 Apr 25;387(1):211-21. doi: 10.1016/j.virol.2009.02.027. Epub 2009 
      Mar 17.