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Publication : Immune protection is dependent on the gut microbiome in a lethal mouse gammaherpesviral infection.

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.
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