Using a Clinically Authentic Mouse Model to Evaluate the Mechanism of Gut Microbiota Influence Enteric Vi Rus Infection and Replication

Recently, the gut microbiota has been demonstrated to be closely associated with human health and disease, including viral infection. Both protection of the host from viral infection and promotion of viral propagation by the microbiota have been reported. The microbiota primes T cells through activation of the inflammasome and then confers protection on the host against influenza virus. The role of microbiota in enterovirus A71 (EV-A71) infection has not yet been studied. Therefore, the interactions of EV-A71 and microbiota were investigated in this project. In this study, the authentic animal model used was developed by intragastrically infecting human SCARB2-transgenic mice (TghSCARB2 mice) with EV-A 71. The feces of TghSCARB2 mice before and on days 3, 5, and 7 after inoculation with EV-A 71 were collected and the microbiota composition was analyzed. The composition of the gut microbiota was significantly altered after EV-A 71 infection, especially 5 and 7 days after infection. In addition, microbial diversity was significantly decreased on day 5 after infection. However, the lethality and disease score in mice with microbiota depleted by treatment with broad-spectrum antibiotics after EV-A 71 infection were significantly increased. Therefore, these results suggested that the microbiota may confer protection on mice against EV-A 71 infection. Aim 1: This project will confirm the roles of intestinal microbiota on EV-A71 infection by using the established strategies of microbiota depletion involving antibiotics and fecal microbiota transplantation in an authentic mouse model. Aim 2: This project will decipher the interactions of the bacterial microbiome, virome, and host and determine the mechanisms of viral pathogenesis and host defense using the functional multi-omics analysis platform. Aim 3: This project will identify potential intestinal commensals against EV-A71 infection and evaluate their efficacy for preventing and treating viral infections. The putative probiotics and postbiotics will be identified and the possible mechanisms will be further deciphered. The identified probiotics and bioactive components will be potential candidates for preventing and treating EV71 infection in the future.

Project ID:PC10907-0884
External Project ID:MOST109-2320-B182-040