title: Pathogenesis of mouse hepatitis virus infection in gamma interferon-deficient mice is modulated by co-infection with Helicobacter hepaticus.
abstract: Gamma interferon-deficient (IFN-gamma KO) mice developed a wasting syndrome and were found to be co-infected with Helicobacter sp., and a new isolate of mouse hepatitis virus (MHV) designated MHV-G. The disease was characterized by pleuritis, peritonitis, hepatitis, pneumonia, and meningitis. Initial experiments used a cecal homogenate inoculum from the clinical cases that contained H. hepaticus and MHV-G to reproduce the development of peritonitis and pleuritis in IFN-gamma KO mice. In contrast, immunocompetent mice given the same inoculum developed an acute, self-limiting infection and remained clinically normal. This result confirmed the importance of IFN-gamma in preventing chronic infection and limiting viral dissemination. To understand the role of both agents in the development of peritonitis and pleuritis, IFN-gamma KO mice were infected with either agent or were co-infected with H. hepaticus and MHV-G. Infection with MHV-G induced a multisystemic infection similar to that described in the original cases, with multifocal hepatic necrosis, acute necrotizing and inflammatory lesions of the gastrointestinal tract, and acute peritonitis and pleuritis with adhesions on the serosal surfaces of the viscera. However, mice given H. hepaticus alone had minimal pathologic changes even though the organism was consistently detected in the cecum or feces. Although co-infection with H. hepaticus and MHV-G induced lesions similar to those associated with MHV-G alone, the pathogenesis of the MHV infection was modified. Helicobacter hepaticus appeared to reduce the severity of MHV-induced lesions during the acute phase of infection, and exacerbated hepatitis and meningitis at the later time point. We conclude that infection of IFN-gamma KO mice with MHV-G results in multisystemic infection with peritonitis, pleuritis, and adhesions due to the aberrant immune response in these mice. In addition, co-infection of these mice with H. hepaticus results in alterations in the pathogenesis of MHV-G infection.
authors.affiliation: Section of Comparative Medicine, Yale University School of Medicine, PO Box 208016, New Haven, Connecticut 06520-8016, USA.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Compton
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Ball-Goodrich
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Zeiss
authors.forename: Linda K
authors.initials: LK
authors.lastname: Johnson
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Johnson
authors.forename: James D
authors.initials: JD
authors.lastname: Macy
mesh_terms: D000818:Animals; D018352:Coronavirus Infections / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D004269:DNA, Bacterial / Q000032:analysis; D016481:Helicobacter Infections / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D044923:Helicobacter hepaticus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D006524:Hepatitis, Viral, Animal; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D006517:Murine hepatitis virus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004269:DNA, Bacterial; D012367:RNA, Viral; D007371:Interferon-gamma