The Human Skin Double-Stranded DNA Virome: Topographical and Temporal Diversity, Genetic Enrichment, and Dynamic Associations with the Host Microbiome

Abstract

Viruses make up a major component of the human microbiota but are poorly understood in the skin, our primary barrier to the external environment. Viral communities have the potential to modulate states of cutaneous health and disease. Bacteriophages are known to influence the structure and function of microbial communities through predation and genetic exchange. Human viruses are associated with skin cancers and a multitude of cutaneous manifestations. Despite these important roles, little is known regarding the human skin virome and its interactions with the host microbiome. Here we evaluated the human cutaneous double-stranded DNA virome by metagenomic sequencing of DNA from purified virus-like particles (VLPs). In parallel, we employed metagenomic sequencing of the total skin microbiome to assess covariation and infer interactions with the virome. Samples were collected from 16 subjects at eight body sites over 1 month. In addition to the microenviroment, which is known to partition the bacterial and fungal microbiota, natural skin occlusion was strongly associated with skin virome community composition. Viral contigs were enriched for genes indicative of a temperate phage replication style and also maintained genes encoding potential antibiotic resistance and virulence factors. CRISPR spacers identified in the bacterial DNA sequences provided a record of phage predation and suggest a mechanism to explain spatial partitioning of skin phage communities. Finally, we modeled the structure of bacterial and phage communities together to reveal a complex microbial environment with a Corynebacterium hub. These results reveal the previously underappreciated diversity, encoded functions, and viral-microbial dynamic unique to the human skin virome.

Skin microbiota–host interactions

“…Other viruses, such as the orthopoxvirus vaccinia virus, are cleared after epicutaneous infection. Although our current understanding of these viruses encompasses only their pathogenic behaviour, analyses of the double-stranded DNA virome have shown that papillomaviruses and poxviruses can also colonize hosts asymptomatically 21,121 . Even in the ‘simple’ case of vaccinia virus, intravital multiphoton microscopy has shown a complex spatial orchestration of immune events; although viral infection occurs in keratinocytes, responding CD8 + T cells do not target the infected keratinocytes but rather innate immune cells 122 .…”

Genomes of Gardnerella Strains Reveal an Abundance of Prophages within the Bladder Microbiome

“…Given this evidence of phage-host interactions and the results of recent studies illuminating the vital contributions of viruses within other human microbiota (e.g. [31,32,41]), one can surmise that phages are playing a significant role within both the bladder and reproductive system communities.…”

Skin Microbiome Surveys Are Strongly Influenced by Experimental Design

“…More recently, whole metagenomic shotgun (WMS) sequencing has been employed for both taxonomic and functional annotation of skin microbial communities (Human Microbiome Project 2012b; Oh et al 2014; Hannigan et al 2015). This approach reduces amplification bias, captures multi-kingdom communities, and allows for strain-level analysis.…”