title: 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.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-1157, USA.
authors.forename: Raghavendran
authors.initials: R
authors.lastname: Kulasegaran-Shylini
authors.forename: Varatharasa
authors.initials: V
authors.lastname: Thiviyanathan
authors.forename: David G
authors.initials: DG
authors.lastname: Gorenstein
authors.forename: Ilya
authors.initials: I
authors.lastname: Frolov
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral / Q000235:genetics*; D051379:Mice; D041681:NIH 3T3 Cells; D014176:Protein Biosynthesis / Q000235:genetics*; D012367:RNA, Viral / Q000096:biosynthesis* / Q000235:genetics; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D020121:5' Untranslated Regions; D012367:RNA, Viral; D014764:Viral Proteins