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 co-evolved virome, a concept with profound implications for understanding health and disease.

Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children

“…No circoviruses have yet been linked to human diseases. Our observation of greater abundance and prevalence of Circoviridae-related sequences in controls suggests that infection with the virus offers benefits to the host, as observed in animal models for other viruses (22)(23)(24) and might offer protection from the development of autoimmune diabetes, as has been shown in animal studies for other types of viruses (25,26). However, the sample size in terms of number of subjects is small in this cohort, and these sequences were not detected in every control subject.…”

“…Because viruses are the fastest-mutating genetic elements on Earth (23), and limitations in the reference viral databases result in the inability to annotate the great majority of sequences present in purified "virus" samples (28,29), we also performed contig-based analysis. Sequences from each sample were individually assembled to minimize the possibility of chimeric sequence formation (27).…”

“…In subject case 3 (E006574), nearly full-length sequences of 10 of the 11 dsRNA segments of a rotavirus genome most closely related to rotavirus A were obtained (Dataset S2). Although the presence of these sequences does not prove infection with the viruses detected, the children were exposed to a broad range of eukaryotic viruses (12,23). We measured virome β diversity using the Hellinger distance metric on the RPKM matrix (34).…”

“…In a recent study, CrAssphage, a human bacteriophage, was correlated with Bacteroides dorei, but a direct association of this virus with islet autoimmunity was not observed (21). Importantly, although it generally has been assumed that viruses cause harm by triggering diseases, studies in animal models show that virus infection is not necessarily harmful and can provide symbiotic benefits (22)(23)(24), and actually may offer protection from the development of T1D (25,26). Thus, an evaluation of the virome in children at risk for T1D might have the potential to identify viruses associated with either disease risk or protection from disease.…”

Organisms or biological individuals? Combining physiological and evolutionary individuality

“…This idea, already expressed by Goethe in 1807 2 , was strengthened by the formulation of the cell theory (by Schwann, Remak and Virchow, in particular) (Duchesneau 1987;Bechtel 2006). Thus, we find Virchow (1978Virchow ( [1858) writing: "What is an organism? A society of living cells, a tiny well-ordered state.…”