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Mol Cell. 2015 Nov 19;60(4):651-60. doi: 10.1016/j.molcel.2015.10.020.

[KIL-d] Protein Element Confers Antiviral Activity via Catastrophic Viral Mutagenesis.

Author information

1
Laboratory for Protein Conformation Diseases, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
2
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.
3
Laboratory for Protein Conformation Diseases, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan. Electronic address: motomasa@brain.riken.jp.

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.

PMID:
26590718
PMCID:
PMC5513702
DOI:
10.1016/j.molcel.2015.10.020
[Indexed for MEDLINE]
Free PMC Article

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