Deciphering the Human Virome with Single-Virus Genomics and Metagenomics

Genomic and metagenomic analyses are increasingly becoming commonplace in several areas of biological research, but recurrent specialized analyses are frequently reported as in-house scripts rarely available after publication. We describe the enveomics collection, a growing set of actively maintained scripts for several recurrent and specialized tasks in microbial genomics and metagenomics, and present a graphical user interface and several case studies. Our resource includes previously described as well as new algorithms such as Transformed-space Resampling In Biased Sets (TRIBS), a novel method to evaluate phylogenetic under- or over-dispersion in reference sets with strong phylogenetic bias. The enveomics collection is freely available under the terms of the Artistic License 2.0 at https://github.com/lmrodriguezr/enveomics and for online analysis at http://enve-omics.ce.gatech.edu

Viral infections have been proposed to elicit pathological processes leading to the initiation of T helper 1 (T H 1) immunity against dietary gluten and celiac disease (CeD). To test this hypothesis and gain insights into mechanisms underlying virus-induced loss of tolerance to dietary antigens, we developed a viral infection model that makes use of two reovirus strains that infect the intestine but differ in their immunopathological outcomes. Reovirus is an avirulent pathogen that elicits protective immunity, but we discovered that it can nonetheless disrupt intestinal immune homeostasis at inductive and effector sites of oral tolerance by suppressing peripheral regulatory T cell (pT reg ) conversion and promoting T H 1 immunity to dietary antigen. Initiation of T H 1 immunity to dietary antigen was dependent on interferon regulatory factor 1 and dissociated from suppression of pT reg conversion, which was mediated by type-1 interferon. Last, our study in humans supports a role for infection with reovirus, a seemingly innocuous virus, in triggering the development of CeD.