A Comprehensive Reference Catalog of Human Skin DNA Virome Reveals Novel Viral Diversity and Microenvironmental Influences

Abstract

IntroductionHuman skin serves as a dynamic habitat for a diverse microbiome, including a complex array of viruses whose diversity and roles are not fully understood. ObjectivesThis study aims to enhance our understanding of this skin viral diversity through the construction of a detailed, non-redundant DNA viral reference catalog. MethodsA total of 2,760 skin metagenomes from six published skin studies were collected. A skin virome catalog was constructed using methods independent of reference databases. Viral characteristics were identified through cross-cohort meta-analysis and used to characterize viral features across different skin environments. ResultsWe identified 20,927 viral sequences, which clustered into 2,873 viral operational taxonomic units (vOTUs). Among these, 2,610 represent previously unrecorded viral sequences, uncovering a substantial breadth of viral diversity on human skin. The results also highlight significant differences in viral communities that are associated with varying skin microenvironments. The oily skin is enriched in Papillomaviridae; the dry skin area is enriched in Autographiviridae, Inoviridae and Mitoviridae; and the moist skin is enriched in Herelleviridae, indicating the adaptive nature of viruses. We also investigated the relationship between bacteriophages and bacteria on the skin surface. We found that skin bacteria such as Pseudomonas, Klebsiella, and Staphylococcus are infected by phages from the class Caudoviricetes. ConclusionThis comprehensive skin DNA viral catalog significantly advances our understanding of the viromes role within the skin ecosystem. The findings highlight the adaptive nature of viruses to different skin microenvironments and their interactions with resident bacteria. This catalog serves as a valuable resource for further epidemiological and therapeutic research, potentially leading to better management and treatment of skin conditions influenced by the skins virome.