Immune protection is dependent on the gut microbiome in a lethal mouse gammaherpesviral infection
| Autor: | Ramani N. Chavan, Efrem S. Lim, Jacquelyn Kilbourne, Jordan R. Yaron, Simona Kraberger, Barbara H. Munk, Juan Maldonado, Arvind Varsani, Amanda M. Tafoya, Erling Olaf Koppang, Scott A. Tibbetts, Alison Stern-Harbutte, Rosa Krajmalnik-Brown, Liqiang Zhang, Shahar Keinan, Whitney Bullard, Alexandra Lucas, Sriram Ambadapadi |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.drug_class viruses Antibiotics lcsh:Medicine Gut flora Article Recombinant protein therapy 03 medical and health sciences Mice 0302 clinical medicine Immune system Virology medicine Animals Interferon gamma Pulmonary pathology Microbiome Lymphocytes Colitis lcsh:Science Lung Serpins Multidisciplinary biology business.industry lcsh:R virus diseases Herpesviridae Infections biochemical phenomena metabolism and nutrition biology.organism_classification medicine.disease Peptide Fragments Recombinant Proteins 3. Good health Anti-Bacterial Agents Gastrointestinal Microbiome 030104 developmental biology Immunology lcsh:Q Vasculitis business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-13 (2020) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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