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Constraints of Viral RNA Synthesis on Codon Usage of Negative-Strand RNA Virus
- Source :
- Journal of virology. 93(5)
- Publication Year :
- 2018
-
Abstract
- Negative-strand RNA viruses (NSVs) include some of the most pathogenic human viruses known. NSVs completely rely on the host cell for protein translation, but their codon usage bias is often different from that of the host. This discrepancy may have originated from the unique mechanism of NSV RNA synthesis in that the genomic RNA sequestered in the nucleocapsid serves as the template. The stability of the genomic RNA in the nucleocapsid appears to regulate its accessibility to the viral RNA polymerase, thus placing constraints on codon usage to balance viral RNA synthesis. By in situ analyses of vesicular stomatitis virus RNA synthesis, specific activities of viral RNA synthesis were correlated with the genomic RNA sequence. It was found that by simply altering the sequence and not the amino acid that it encoded, a significant reduction, up to an ∼750-fold reduction, in viral RNA transcripts occurred. Through subsequent sequence analysis and thermal shift assays, it was found that the purine/pyrimidine content modulates the overall stability of the polymerase complex, resulting in alteration of the activity of viral RNA synthesis. The codon usage is therefore constrained by the obligation of the NSV genome for viral RNA synthesis. IMPORTANCE Negative-strand RNA viruses (NSVs) include the most pathogenic viruses known. New methods to monitor their evolutionary trends are urgently needed for the development of antivirals and vaccines. The protein translation machinery of the host cell is currently recognized as a main genomic regulator of RNA virus evolution, which works especially well for positive-strand RNA viruses. However, this approach fails for NSVs because it does not consider the unique mechanism of their viral RNA synthesis. For NSVs, the viral RNA-dependent RNA polymerase (vRdRp) must gain access to the genome sequestered in the nucleocapsid. Our work suggests a paradigm shift that the interactions between the RNA genome and the nucleocapsid protein regulate the activity of vRdRp, which selects codon usage.
- Subjects :
- Sequence analysis
viruses
Immunology
Genome, Viral
Virus Replication
Microbiology
Genome
Vesicular stomatitis Indiana virus
Cell Line
03 medical and health sciences
chemistry.chemical_compound
Virology
RNA polymerase
Cricetinae
Animals
Codon
Polymerase
030304 developmental biology
Genetics
0303 health sciences
biology
Base Sequence
030306 microbiology
Sequence Analysis, RNA
Structure and Assembly
RNA
RNA virus
Nucleocapsid Proteins
biology.organism_classification
chemistry
Vesicular stomatitis virus
Insect Science
Codon usage bias
Protein Biosynthesis
biology.protein
RNA, Viral
Subjects
Details
- ISSN :
- 10985514
- Volume :
- 93
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Journal of virology
- Accession number :
- edsair.doi.dedup.....de0f09fefe21121f57a96e93b0f8c6da