An archaeal CBASS system eliminates viruses without killing the host cells

Abstract Many CBASS systems defend against viral infections by depleting cellular NAD+ levels, eventually leading to 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, in chronic viral infections, which often occur in archaea, abortive infection could be detrimental, as the cost of immunity may outweigh that of infection. Here we study an archaeal CBASS system that was expressed in the model organism Haloferax volcanii DS2. We demonstrate that this system protects against a chronically infecting virus, HFPV-1, and eliminates the virus after several passages without killing the host. Moreover, cells that cleared the virus become substantially more resistant to subsequent HFPV-1 infections. Cell death only occurs after extensive incubation with HFPV-1. These findings suggest that CBASS can also be beneficial during non-lytic infections, potentially explaining why such systems are relatively common in archaea.