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

Research output: Contribution to journalArticle

Authors

  • Jordan R. Yaron
  • Sriram Ambadapadi
  • Liqiang Zhang
  • Ramani N. Chavan
  • Scott A. Tibbetts
  • Shahar Keinan
  • Arvind Varsani
  • Juan Maldonado
  • Simona Kraberger
  • Amanda M. Tafoya
  • Whitney L. Bullard
  • Jacquelyn Kilbourne
  • Alison Stern-Harbutte
  • Rosa Krajmalnik-Brown
  • Barbara H. Munk
  • Erling O. Koppang
  • Efrem S. Lim
  • Alexandra R. Lucas

External Institution(s)

  • Arizona State University
  • University of Florida
  • Research Triangle
  • University of Cape Town
  • Norwegian University of Life Sciences

Details

Original languageEnglish (US)
Article number2371
JournalScientific reports
Volume10
Issue number1
StatusPublished - Dec 1 2020
Peer-reviewedYes

Abstract

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.

Citation formats

APA

Yaron, J. R., Ambadapadi, S., Zhang, L., Chavan, R. N., Tibbetts, S. A., Keinan, S., ... Lucas, A. R. (2020). Immune protection is dependent on the gut microbiome in a lethal mouse gammaherpesviral infection. Scientific reports, 10(1), [2371]. https://doi.org/10.1038/s41598-020-59269-9

Harvard

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 2020, 'Immune protection is dependent on the gut microbiome in a lethal mouse gammaherpesviral infection', Scientific reports, vol. 10, no. 1, 2371. https://doi.org/10.1038/s41598-020-59269-9