Murine viral hepatitis involves NK cell depletion associated with virus-induced apoptosis.
Mouse hepatitis virus type 3 (MHV3), a coronavirus, is an excellent animal model for the study of immunological disorders related to acute and chronic hepatitis. In this study, we have verified if the fulminant hepatitis induced by MHV3 could be related to an impairment of innate immunity. Groups of three C57BL/6 mice were infected with the pathogenic L2-MHV3 or attenuated YAC-MHV3 viruses, and the natural killer (NK) cell populations from liver, spleen and bone marrow were analysed. The percentage of intrahepatic NK1.1(+)T cell receptor (TCR)- cells did not increase while NK1.1(+)TCR(inter) cells decreased in both L2-MHV3- and YAC-MHV3-infected mice. Concurrently, splenic and myeloid NK1.1+ cells decreased in L2-MHV3-infected mice. However, the cytotoxic activity of NK cells increased in liver and decreased in bone marrow from pathogenic L2-MHV3-infected mice while no modification was detected in YAC-MHV3-infected mice. Flow cytometric analysis revealed that both normal and larger splenic or myeloid NK cells decreased more in pathogenic L2-MHV3-infected mice than in attenuated YAC-MHV3-infected mice. In vitro viral infections of interleukin (IL)-15-stimulated lymphoid cells from liver and bone marrow revealed that L2-MHV3 induced higher decreases in cell viability of NK1.1+ cells than the YAC-MHV3 variant. The NK cell decreases were due to the viral permissivity leading to cytopathic effects characterized by cell rounding, syncytia formation and apoptosis. Larger NK+ syncytia were observed in L2-MHV3-infected cells than in YAC-MHV3-infected cells. These results suggest that NK cell production is impaired by viral infection favouring fulminant hepatitis.
Lehoux
M
M
Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Canada.
Jacques
A
A
Lusignan
S
S
Lamontagne
L
L
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D002460:Cell Line; D018352:Coronavirus Infections / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D006524:Hepatitis, Viral, Animal / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D019409:Interleukin-15 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D006517:Murine hepatitis virus / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013154:Spleen / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
D019409:Interleukin-15; D016693:Receptors, Antigen, T-Cell, alpha-beta