Genomic insights into antiviral defense systems in haloarchaea and their impact on virus susceptibility

The ongoing evolutionary arm race between archaea and their viruses has led to the development of diverse defense systems against viruses. While recent computational approaches have uncovered many bacterial antiviral defense systems, the viral infection strategies and antiviral responses of archaea remain poorly explored. In this study, we identified antiviral defense systems encoded in the genomes of 20 recently sequenced haloarchaeal strains. These systems were found to be representative of the broader repertoire of defense systems present across all 253 complete sequenced Halobacteria (class) genomes in the RefSeq database. Detailed analysis showed that these haloarchaea usually harbor multiple different defense systems, with a particularly high abundance of uncharacterized predicted defense systems against viruses (Phage Defense Candidates (PDCs)). To further explore the impact of anti-viral defense mechanisms on host range, an extensive virus-host pair screening was performed using a panel of known virulent viruses. By correlating the genomic defense profiles with observed viral infectivity and adsorption profiles, a weak correlation between the number of encoded defense systems and viral susceptibility was detected. Specifically, hosts infected by fewer viruses tended to encode a broader repertoire of antiviral defense systems, whereas those with fewer defense systems were frequently infected. It was found that the host range of haloarchaeal viruses is majorly determined by the availability of viral receptors, whereas the presence of anti-viral defense systems plays a smaller but significant role. These findings offer valuable insights into the evolutionary pressure shaping archaeal antiviral strategies and lay the groundwork for future functional studies of archaeal defense systems. ImportanceArchaeal viruses are understudied, compared to viruses infecting bacteria and eukaryotes. Haloarchaea have evolved as model organisms for the study of virus-host interaction in archaea, as they harbor the highest number of isolated archaeal viruses. Salt-loving haloarchaea dominate microbial communities in hypersaline environments, where they face constant viral threats. To survive, they have evolved a diverse array of antiviral defense systems. Until now, the relevance of these defense systems for susceptibility to viruses had not been tested in archaea. The findings of this study show that strains with a broader repertoire of defense systems tend to be less susceptible to viral infection, while those with fewer systems are more frequently targeted, suggesting an advantage for the accumulation of different defense systems. In addition, it was found that the major determinant of host range is the availability of viral receptors on the host cell. These insights provide a foundation for future research into the molecular mechanisms and ecological roles of archaeal defense systems.