Diverse defense systems synergistically drive the microbe-virus arms race in deep sea cold seeps

Cold seeps are unique deep-sea ecosystems that host diverse uncharacterized microbes and viruses, many of which potentially possess novel defense and counter-defense systems. Despite their ecological significance, the diversity of microbial defense systems, their interactions, and the evolutionary arms race with viral anti-defense strategies in cold seeps remain largely unexplored. To address this, we analyzed 3,813 microbial and 13,336 viral genomes from 193 metagenomic samples collected across 17 cold seep sites. Cold seep microbes harbor an extensive repertoire of ‘defense systems (n = 26,389), with 63% representing novel systems. Laboratory experiments confirm that several of these novel systems effectively protect against viral infections. These defense systems frequently co-occur and interact synergistically to combat viral infections. They are widely distributed across different sediment depths and geographical locations, exhibiting active expression. In response, cold seep viruses have evolved a diverse array of anti-defense genes (n = 1,197), employing complex strategies to counteract host defenses. The concurrent presence of multiple viral anti-defense genes and various microbial defense genes in their hosts highlights the intricate and dynamic interactions between viruses and their microbial counterparts. Functionally critical lineages, such as anaerobic methanotrophic archaea (ANME), sulfate-reducing bacteria (SRB), and diazotrophs, adapt their defensive strategies according to ecological niches and environmental pressures. Notably, SRB strains were found to harbor multiple Gabija defense systems, enhancing their resistance to viral attacks, while corresponding viruses carry anti-Gabija genes, illustrating a specific evolutionary adaptation. Overall, these findings underscore the critical role of virus-microbe interactions in shaping microbial metabolic functions and environmental adaptation in extreme deep-sea subseafloor environments.