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 B. Hogue,
Whitney L. Bullard,
Scott Tibbetts,
Alexandra R. Lucas
Affiliations
Hao Chen
Department of Medicine, Divisions of Cardiovascular Medicine and Rheumatology, University of Florida, Gainesville, FL 32610-0277, USA
Mee Yong Bartee
Department of Medicine, Divisions of Cardiovascular Medicine and Rheumatology, University of Florida, Gainesville, FL 32610-0277, USA
Jordan R. Yaron
Centers for Personalized Diagnostics and Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287-6401, USA
Liying Liu
Department of Surgery, BIDMC, Harvard Medical School, Boston, MA 02115, USA
Liqiang Zhang
Centers for Personalized Diagnostics and Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287-6401, USA
Donghang Zheng
Department of Medicine, Divisions of Cardiovascular Medicine and Rheumatology, University of Florida, Gainesville, FL 32610-0277, USA
Ian B. Hogue
Centers for Personalized Diagnostics and Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287-6401, USA
Whitney L. Bullard
Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA
Scott Tibbetts
Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA
Alexandra R. Lucas
Department of Medicine, Divisions of Cardiovascular Medicine and Rheumatology, University of Florida, Gainesville, FL 32610-0277, USA
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.
