The virome in mammalian physiology and disease

Abstract

The virome contains the most abundant and fastest mutating genetic elements on Earth. The mammalian virome is constituted of viruses that infect host cells, virus-derived elements in our chromosomes, and viruses that infect the broad array of other types of organisms that inhabit us. Virome interactions with the host cannot be encompassed by a monotheistic view of viruses as pathogens. Instead, the genetic and transcriptional identity of mammals is defined in part by our coevolved virome, a concept with profound implications for understanding health and disease.

Figure 1. Components of the virome and their relationship to the genotype/phenotype relationship

The mammalian virome changes rapidly over time through both exchange of viruses with other organisms and through evolution of the individual viruses that constitute the virome. The major components of the virome are the eukaryotic virome, endogenous viral elements, and the prokaryotic virome which includes viruses of both bacteria and archaea. Members of the virome influence the phenotype of the host in a combinatorial manner by interacting with other members of the microbiome (such as other members of the virome itself, the bacterial microbiome, the mycobiome, or the meiofauna) and by interacting with individual variations in host genetics. Together these interactions may influence a range of phenotypes, shown on the right, important for health and disease.

Figure 2. One possible mechanism for the influence of the virome on host phenotype

Since the virome differs between individuals, and since multiple sensors of viral infection can induce overlapping but distinct transcriptional effects, the virome of asymptomatic individuals may play an important role in regulating the transcriptional state of healthy people. This transcriptional state is referred to as the immunophenotype of the host in the text. Individuals may then respond to triggers of disease in different ways in a manner dependent on the nature of their individual viromes and genetic constitution.