First Author | Yaron JR | Year | 2020 |
Journal | Sci Rep | Volume | 10 |
Issue | 1 | Pages | 2371 |
PubMed ID | 32047224 | Mgi Jnum | J:292996 |
Mgi Id | MGI:6407260 | Doi | 10.1038/s41598-020-59269-9 |
Citation | Yaron JR, et al. (2020) Immune protection is dependent on the gut microbiome in a lethal mouse gammaherpesviral infection. Sci Rep 10(1):2371 |
abstractText | 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 (IFNgammaR(-/-)) 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. |