Coexistence of virome-encoded health-associated genes and pathogenic genes in global habitats.

Viral remnants constitute approximately 8% of the human genome, reflecting extensive historical gene exchange between viruses and their hosts. Some viral genomes harbor genes acquired through horizontal gene transfer that are associated with potential benefits to human health, alongside genes associated with pathogenicity. However, their global distribution, functional characteristics, and coexistence patterns remain poorly understood. Here, using the Integrated Microbial Genomes and Virome (IMG/VR v4) database, we identified 4,556 viruses carrying gene segments associated with human health across eight habitat types spanning 13 regions and 76 countries worldwide. Among viruses with identifiable hosts, those distributed in humans (478) accounted for the highest proportion. The viral genes associated with human health included IMPORTANCE: Viruses are the most abundant biological entities on Earth and key drivers of microbial evolution through horizontal gene transfer. While often studied for their pathogenic effects, viruses can also carry genes that influence host metabolism and health. Genes associated with human health have been identified in viral genomes, yet their global distribution, functions, and coexistence with pathogenic genes remain largely unexplored. This study integrates datasets of health-associated genes into viral genomic analyses, revealing for the first time the coexistence of viral health-associated genes with those linked to pathogenicity. This dual genetic potential is observed across diverse habitats, highlighting viruses as multifaceted reservoirs of both beneficial and harmful genes. The study findings advance understanding of viral functional diversity and open new avenues for exploring viral roles in microbial ecology, biotechnology, and human health.