Mouse gamma herpesvirus MHV-68 induces severe gastrointestinal (GI) dilatation in interferon gamma receptor-deficient mice (IFNγR−/−) that is blocked by interleukin-10

Hao Chen, Mee Yong Bartee, Jordan R. Yaron, Liying Liu, Liqiang Zhang, Donghang Zheng, Ian Hogue, Whitney L. Bullard, Scott Tibbetts, Alexandra R. Lucas

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Inflammatory bowel disease (IBD) and Clostridium difficile infection cause gastrointestinal (GI) distension and, in severe cases, toxic megacolon with risk of perforation and death. Herpesviruses have been linked to severe GI dilatation. MHV-68 is a model for human gamma herpesvirus infection inducing GI dilatation in interleukin-10 (IL-10)-deficient mice but is benign in wildtype mice. MHV-68 also causes lethal vasculitis and pulmonary hemorrhage in interferon gamma receptor-deficient (IFNγR−/−) mice, but GI dilatation has not been reported. In prior work the Myxomavirus-derived anti-inflammatory serpin, Serp-1, improved survival, reducing vasculitis and pulmonary hemorrhage in MHV-68-infected IFNγR−/− mice with significantly increased IL-10. IL-10 has been investigated as treatment for GI dilatation with variable efficacy. We report here that MHV-68 infection produces severe GI dilatation with inflammation and gut wall degradation in 28% of INFγR-/- mice. Macrophage invasion and smooth muscle degradation were accompanied by decreased concentrations of T helper (Th2), B, monocyte, and dendritic cells. Plasma and spleen IL-10 were significantly reduced in mice with GI dilatation, while interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor alpha (TNFα) and INFγ increased. Treatment of gamma herpesvirus-infected mice with exogenous IL-10 prevents severe GI inflammation and dilatation, suggesting benefit for herpesvirus-induced dilatation.

Original languageEnglish (US)
Article number518
JournalViruses
Volume10
Issue number10
DOIs
StatePublished - Oct 2018

Keywords

  • Gamma herpesvirus
  • Gastrointestinal
  • Interleukin-10
  • MHV-68
  • Macrophage
  • Toxic megacolon

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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