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
| Autor: | Raghavendran Kulasegaran-Shylini, Varatharasa Thiviyanathan, Ilya Frolov, David G. Gorenstein |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Gene Expression Regulation
Viral Five prime untranslated region Alphavirus Genome Viral medicine.disease_cause Virus Replication Article Cell Line Encephalitis Virus Venezuelan Equine 5′UTR 03 medical and health sciences Mice Viral Proteins Transcription (biology) Virology Cricetinae Attenuating mutation medicine Animals RNA synthesis 030304 developmental biology Subgenomic mRNA Genetics 0303 health sciences biology 030306 microbiology RNA RNA secondary structure biology.organism_classification NMR 3. Good health Viral replication Protein Biosynthesis Venezuelan equine encephalitis virus Togaviridae NIH 3T3 Cells RNA Viral 5' Untranslated Regions |
| Zdroj: | Virology. 387(1) |
| ISSN: | 1096-0341 |
| Popis: | 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-α/β suggest a plausible explanation for its attenuated phenotype. |
| Databáze: | OpenAIRE |
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