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 journalArticle

1 Citation (Scopus)

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 1 2018

Fingerprint

Herpesviridae
Interleukin-10
Dilatation
Vasculitis
Toxic Megacolon
Hemorrhage
Serpins
Inflammation
Clostridium Infections
Herpesviridae Infections
Lung
Clostridium difficile
interferon gamma receptor
Interleukin-1beta
Inflammatory Bowel Diseases
Dendritic Cells
Smooth Muscle
Monocytes
Interleukin-6
Anti-Inflammatory Agents

Keywords

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

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

Cite this

Mouse gamma herpesvirus MHV-68 induces severe gastrointestinal (GI) dilatation in interferon gamma receptor-deficient mice (IFNγR−/−) that is blocked by interleukin-10. / Chen, Hao; Bartee, Mee Yong; Yaron, Jordan R.; Liu, Liying; Zhang, Liqiang; Zheng, Donghang; Hogue, Ian; Bullard, Whitney L.; Tibbetts, Scott; Lucas, Alexandra R.

In: Viruses, Vol. 10, No. 10, 518, 01.10.2018.

Research output: Contribution to journalArticle

Chen, Hao ; Bartee, Mee Yong ; Yaron, Jordan R. ; Liu, Liying ; Zhang, Liqiang ; Zheng, Donghang ; Hogue, Ian ; Bullard, Whitney L. ; Tibbetts, Scott ; Lucas, Alexandra R. / Mouse gamma herpesvirus MHV-68 induces severe gastrointestinal (GI) dilatation in interferon gamma receptor-deficient mice (IFNγR−/−) that is blocked by interleukin-10. In: Viruses. 2018 ; Vol. 10, No. 10.
@article{c0ca82e0fba24234a039073a0738c291,
title = "Mouse gamma herpesvirus MHV-68 induces severe gastrointestinal (GI) dilatation in interferon gamma receptor-deficient mice (IFNγR−/−) that is blocked by interleukin-10",
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.",
keywords = "Gamma herpesvirus, Gastrointestinal, Interleukin-10, Macrophage, MHV-68, Toxic megacolon",
author = "Hao Chen and Bartee, {Mee Yong} and Yaron, {Jordan R.} and Liying Liu and Liqiang Zhang and Donghang Zheng and Ian Hogue and Bullard, {Whitney L.} and Scott Tibbetts and Lucas, {Alexandra R.}",
year = "2018",
month = "10",
day = "1",
doi = "10.3390/v10100518",
language = "English (US)",
volume = "10",
journal = "Viruses",
issn = "1999-4915",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "10",

}

TY - JOUR

T1 - Mouse gamma herpesvirus MHV-68 induces severe gastrointestinal (GI) dilatation in interferon gamma receptor-deficient mice (IFNγR−/−) that is blocked by interleukin-10

AU - Chen, Hao

AU - Bartee, Mee Yong

AU - Yaron, Jordan R.

AU - Liu, Liying

AU - Zhang, Liqiang

AU - Zheng, Donghang

AU - Hogue, Ian

AU - Bullard, Whitney L.

AU - Tibbetts, Scott

AU - Lucas, Alexandra R.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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.

AB - 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.

KW - Gamma herpesvirus

KW - Gastrointestinal

KW - Interleukin-10

KW - Macrophage

KW - MHV-68

KW - Toxic megacolon

UR - http://www.scopus.com/inward/record.url?scp=85053822988&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053822988&partnerID=8YFLogxK

U2 - 10.3390/v10100518

DO - 10.3390/v10100518

M3 - Article

VL - 10

JO - Viruses

JF - Viruses

SN - 1999-4915

IS - 10

M1 - 518

ER -