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Mouse Gamma Herpesvirus MHV-68 Induces Severe Gastrointestinal (GI) Dilatation in Interferon Gamma Receptor-Deficient Mice (IFNγR−/−) That Is Blocked by Interleukin-10

1
Department of Medicine, Divisions of Cardiovascular Medicine and Rheumatology, University of Florida, Gainesville, FL 32610-0277, USA
2
Centers for Personalized Diagnostics and Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287-6401, USA
3
Department of Surgery, BIDMC, Harvard Medical School, Boston, MA 02115, USA
4
Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA
*
Authors to whom correspondence should be addressed.
Viruses 2018, 10(10), 518; https://doi.org/10.3390/v10100518
Received: 31 July 2018 / Revised: 9 September 2018 / Accepted: 21 September 2018 / Published: 23 September 2018
(This article belongs to the Special Issue Cytokine Responses in Viral Infections)
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. View Full-Text
Keywords: MHV-68; gamma herpesvirus; Interleukin-10; macrophage; gastrointestinal; toxic megacolon MHV-68; gamma herpesvirus; Interleukin-10; macrophage; gastrointestinal; toxic megacolon
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Chen, H.; Bartee, M.Y.; Yaron, J.R.; Liu, L.; Zhang, L.; Zheng, D.; Hogue, I.B.; Bullard, W.L.; Tibbetts, S.; Lucas, A.R. Mouse Gamma Herpesvirus MHV-68 Induces Severe Gastrointestinal (GI) Dilatation in Interferon Gamma Receptor-Deficient Mice (IFNγR−/−) That Is Blocked by Interleukin-10. Viruses 2018, 10, 518.

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