Cold seeps are globally distributed deep-sea ecosystems harboring diverse chemosynthetic microbial communities, yet their viral components remain poorly understood. Here, we establish the Global Cold Seep Virome, a comprehensive catalog of 191,937 species-level viral operational taxonomic units (vOTUs) and 2.44 million viral protein clusters reconstructed from 314 metagenomes spanning 18 cold seep sites worldwide. Most vOTUs are distinct from those in existing environmental viromes, suggesting that cold seeps harbor a largely unexplored viral reservoir. Host prediction identified diverse viral associations with key prokaryotes such as anaerobic methanotrophic archaea, while protein annotation further reveals widespread uncharacterized proteins and ecologically specialized hallmark genes. We also identify putative auxiliary metabolic genes, anti-defense proteins, and lysins, and experimentally validate representative anti-defense proteins and lysins with strong activities. This resource expands current knowledge of deep-sea viral diversity and provides a foundation for studying virus-host interactions, biogeochemistry, and biotechnological potential in cold seep ecosystems.
 

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