[KIL-d] Protein Element Confers Antiviral Activity via Catastrophic Viral Mutagenesis
| Autor: | Motomasa Tanaka, Jonathan S. Weissman, Genjiro Suzuki |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Gene Expression Regulation
Viral viruses Mutagenesis (molecular biology technique) Biology Virus Replication medicine.disease_cause Antiviral Agents Article Virus Fungal Proteins Viral Proteins Viral entry medicine Molecular Biology Gene RNA Double-Stranded Fungal protein Mutation High-Throughput Nucleotide Sequencing RNA Sequence Analysis DNA Cell Biology Virology Viral replication RNA Viral |
| Zdroj: | Molecular Cell. 60:651-660 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2015.10.020 |
| Popis: | Eukaryotic cells are targeted by pathogenic viruses and have developed cell defense mechanisms against viral infection. In yeast, the cellular extrachromosomal genetic element [KIL-d] alters killer activity of M double-stranded RNA killer virus and confers cell resistance against the killer virus. However, its underlying mechanism and the molecular nature of [KIL-d] are unknown. Here, we demonstrate that [KIL-d] is a proteinaceous prion-like aggregate with non-Mendelian cytoplasmic transmission. Deep sequencing analyses revealed that [KIL-d] selectively increases the rate of de novo mutation in the killer toxin gene of the viral genome, producing yeast harboring a defective mutant killer virus with a selective growth advantage over those with WT killer virus. These results suggest that a prion-like [KIL-d] element reprograms the viral replication machinery to induce mutagenesis and genomic inactivation via the long-hypothesized mechanism of "error catastrophe." The findings also support a role for prion-like protein aggregates in cellular defense and adaptation. |
| Databáze: | OpenAIRE |
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