Project description:Ulcerative colitis is a chronic inflammatory disorder for which a definitive cure is still missing. This is characterized by an overwhelming inflammatory milieu in the colonic tract where a composite set of immune and non-immune cells orchestrate its pathogenesis. Over the last years, a growing body of evidence has been pinpointing gut virome dysbiosis as underlying its progression. Nonetheless, its role during the early phases of chronic inflammation is far from being fully defined. Here we show the gut virome-associated Hepatitis B virus protein X, most likely acquired after an event of zoonotic spillover, to be associated with the early stages of ulcerative colitis and to induce colonic inflammation in mice. It acts as a transcriptional regulator in epithelial cells, provoking barrier leakage and altering mucosal immunity at the level of both innate and adaptive immunity. This study paves the way to the comprehension of the aetiopathogenesis of intestinal inflammation and encourages further investigations of the virome as a trigger also in other scenarios. Moreover, it provides a brand-new standpoint that looks at the virome as a target for tailored treatments, blocking the early phases of chronic inflammation and possibly leading to better disease management.
Project description:Contributions of the viral component of the microbiome, the virome, to the development of innate and adaptive immunity are largely unknown. In this study, we systematically defined the tissue host response to a panel of eukaryotic enteric viruses inducing asymptomatic infection in mice. Small intestinal and colon transcriptomes from GF mice were compared to the ones from germ-free mice mono-infected with each of the viruses in the panel. This transcriptional profiling unveiled general adaptations by the host as well as numerous viral strain-specific responses that persist.