An adenine-to-guanine nucleotide change in the IRES SL-IV domain of picornavirus/hepatitis C chimeric viruses leads to a nonviable phenotype
| Autor: | Beverly A. Heinz, Kevin L McKnight, Stephanie L. Sandefur, Krista M Phipps |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Gene Expression Regulation
Viral Guanine Picornavirus Transcription Genetic viruses Hepatitis C virus Molecular Sequence Data Hepacivirus Picornaviridae Viral Plaque Assay medicine.disease_cause Transfection Virus Virology Mengovirus medicine Animals Humans Recombination Genetic biology Base Sequence Poliovirus Adenine fungi virus diseases biology.organism_classification Molecular biology digestive system diseases NS2-3 protease Internal ribosome entry site Viral replication Protein Biosynthesis Mutation Nucleic Acid Conformation RNA Viral Cattle Ribosomes HeLa Cells |
| Zdroj: | Virology. 317(2):345-358 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2003.08.033 |
| Popis: | The inability for the internal ribosomal entry site (IRES) of hepatitis C virus (HCV) to be readily studied in the context of viral replication has been circumvented by constructing chimeras such as with poliovirus (PV), in which translation of the genome polyprotein is under control of the HCV IRES. During our attempts to configure the PV/HCV chimera for our drug discovery efforts, we discovered that an adenine- (A) to-guanine (G) change at nt 350 in domain IV of the HCV IRES resulted in a nonviable phenotype. Similarly, a mengovirus (MV)/HCV chimera using the same configuration with a G at nt 350 (G-350) was found to be nonviable. In contrast, a bovine viral diarrhea virus (BVDV)/HCV chimera remained viable with G-350 in the HCV IRES insert. Second-site, resuscitating mutations were identified from the G-350 PV/HCV and MV/HCV viruses after blind passaging. For both viruses, the resuscitating mutations involved destabilization of domain IV in the HCV IRES. The nonviability of G-350 in the picornavirus/HCV chimeric background might be linked to translation efficiency as indicated by analyses with dual reporter and PV/HCV replicon constructs. |
| Databáze: | OpenAIRE |
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