An archaeal CBASS system eliminates viruses without killing the host cells

Abstract

Many cyclic-oligonucleotide-based antiphage signalling systems (CBASS) defend against viral infections using a TIR-SAVED domain protein that depletes cellular NAD+ levels, eventually leading to cell dormancy or death. This abortive infection strategy is beneficial in stopping fast lytic infections, as cells die before spreading the virus to neighboring cells. However, many archaea are infected by chronic "temperate" viruses that coexist with their hosts for extended periods. In such situations, abortive infection could be detrimental, as the cost of immunity may outweigh that of infection. In this study, we examine an archaeal Type II-C CBASS system from Haloferax strain Atlit 48N that was heterologously expressed in the model organism Haloferax volcanii DS2. We demonstrate that this system protects against a chronically infecting virus, HFPV-1, and enables clearing of the virus after several passages without killing the host. Moreover, cells that have cleared the virus become substantially more resistant to future HFPV-1 infections, without acquiring CRISPR spacers from that virus. Cell death during viral infection only occurs after extensive incubation with HFPV-1. These findings suggest that CBASS could be beneficial even for archaea exposed to chronic infecting viruses, potentially explaining why such systems are relatively common in archaea.