title: [KIL-d] Protein Element Confers Antiviral Activity via Catastrophic Viral Mutagenesis.
abstract: 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.
authors.affiliation: Laboratory for Protein Conformation Diseases, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Genjiro
authors.initials: G
authors.lastname: Suzuki
authors.affiliation: Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Center for RNA Systems Biology, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Weissman
authors.affiliation: Laboratory for Protein Conformation Diseases, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan. Electronic address: motomasa@brain.riken.jp.
authors.forename: Motomasa
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D059014:High-Throughput Nucleotide Sequencing; D009154:Mutation; D012330:RNA, Double-Stranded / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D005656:Fungal Proteins; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D014764:Viral Proteins