NIST/IBBR Seminar: Ring War: virus-host conflict involving Type III CRISPR defence

All living things are subject to attack by viruses. Cells have evolved many different immune systems to protect themselves, including the adaptive and innate immune systems of vertebrates and the CRISPR and restriction:modification systems of bacteria. Viruses have developed potent countermeasures to subvert these systems, and this perpetual arms race has been a strong driving force in evolution throughout the history of life on Earth. The CRISPR system is an adaptive immune system in prokaryotes. Type III CRISPR systems confer a complex, multi-layered defence against viruses. Detection of foreign RNA leads the Cas10 subunit of type III systems to generate the second messenger cyclic oligoadenylate (cOA), which sculpts the cellular response to infection. cOA activates a range of effector proteins, including the ribonuclease Csm6/Csx1, which degrades RNA non-specifically to slow down both viral and host metabolism and “buy some time”. Some organisms encode a dedicated “Ring nuclease” which degrades the cOA signal and returns cells to an uninfected state following viral RNA clearance. This presentation will explore the mechanisms and diversity of cOA-activated effector proteins, and viral counter-measures, in type III CRISPR systems from bacteria and archaea.