Immune protection is dependent on the gut microbiome in a lethal mouse gammaherpesviral infection.
Sci Rep. 2020 Feb 11;10(1):2371
Authors: Yaron JR, Ambadapadi S, Zhang L, Chavan RN, Tibbetts SA, Keinan S, Varsani A, Maldonado J, Kraberger S, Tafoya AM, Bullard WL, Kilbourne J, Stern-Harbutte A, Krajmalnik-Brown R, Munk BH, Koppang EO, Lim ES, Lucas AR
Immunopathogenesis in systemic viral infections can induce a septic state with leaky capillary syndrome, disseminated coagulopathy, and high mortality with limited treatment options. Murine gammaherpesvirus-68 (MHV-68) intraperitoneal infection is a gammaherpesvirus model for producing severe vasculitis, colitis and lethal hemorrhagic pneumonia in interferon gamma receptor-deficient (IFNγR-/-) mice. In prior work, treatment with myxomavirus-derived Serp-1 or a derivative peptide S-7 (G305TTASSDTAITLIPR319) induced immune protection, reduced disease severity and improved survival after MHV-68 infection. Here, we investigate the gut bacterial microbiome in MHV-68 infection. Antibiotic suppression markedly accelerated MHV-68 pathology causing pulmonary consolidation and hemorrhage, increased mortality and specific modification of gut microbiota. Serp-1 and S-7 reduced pulmonary pathology and detectable MHV-68 with increased CD3 and CD8 cells. Treatment efficacy was lost after antibiotic treatments with associated specific changes in the gut bacterial microbiota. In summary, transkingdom host-virus-microbiome interactions in gammaherpesvirus infection influences gammaherpesviral infection severity and reduces immune modulating therapeutic efficacy.
PMID: 32047224 [PubMed – in process]