Authors: | Meeske, A. J.; Jia, N.; Cassel, A. K.; Kozlova, A.; Liao, J.; Wiedmann, M.; Patel, D. J.; Marraffini, L. A. |
Article Title: | A phage-encoded anti-CRISPR enables complete evasion of type VI-A CRISPR-Cas immunity |
Abstract: | The CRISPR RNA (crRNA)-guided nuclease Cas13 recognizes complementary viral transcripts to trigger the degradation of both host and viral RNA during the type VI CRISPR-Cas antiviral response. However, how viruses can counteract this immunity is not known. We describe a listeriaphage (φLS46) encoding an anti-CRISPR protein (AcrVIA1) that inactivates the type VI-A CRISPR system of Listeria seeligeri Using genetics, biochemistry, and structural biology, we found that AcrVIA1 interacts with the guide-exposed face of Cas13a, preventing access to the target RNA and the conformational changes required for nuclease activation. Unlike inhibitors of DNA-cleaving Cas nucleases, which cause limited immunosuppression and require multiple infections to bypass CRISPR defenses, a single dose of AcrVIA1 delivered by an individual virion completely dismantles type VI-A CRISPR-mediated immunity. Copyright © 2020, American Association for the Advancement of Science. |
Keywords: | genetics; metabolism; virology; virus rna; rna stability; endonuclease; rna, viral; dna cleavage; viral proteins; crispr-associated proteins; bacteriophage; endonucleases; bacteriophages; guide rna; rna, guide; listeria; crispr associated protein; clustered regularly interspaced short palindromic repeat; crispr cas system; crispr-cas systems; clustered regularly interspaced short palindromic repeats; viral protein |
Journal Title: | Science |
Volume: | 369 |
Issue: | 6499 |
ISSN: | 0036-8075 |
Publisher: | American Association for the Advancement of Science |
Date Published: | 2020-07-03 |
Start Page: | 54 |
End Page: | 59 |
Language: | English |
DOI: | 10.1126/science.abb6151 |
PUBMED: | 32467331 |
PROVIDER: | scopus |
PMCID: | PMC7975689 |
DOI/URL: | |
Notes: | Article -- Export Date: 3 August 2020 -- Source: Scopus |