Interaction of mouse hepatitis virus 3 with Kupffer cells explanted from susceptible and resistant mouse strains. Antiviral activity, interleukin-1 synthesis.
The genetic sensitivity of mouse strains to mouse hepatitis virus 3 (MHV 3) has been related in vitro to a delay of virus replication in liver sinusoidal cells. In vivo immuno-histochemical studies of the liver from infected mice have demonstrated that mechanisms other than direct viral injury are in operation. To examine potential mechanisms, the interaction of lipopolysaccharide (LPS)-stimulated Kupffer cells with MHV 3 was studied. We first observed a dramatic inhibition in viral replication in LPS-treated Kupffer cells explanted from A/J resistant mice. Second, we demonstrated that MHV 3 induced a dose-dependent interleukin 1 (IL-1) activity in the supernatants of infected Kupffer cells of both strains. These results led us finally to examine the antigen-processing function of the Kupffer cells of both strains of mice. No striking differences were observed in the ability of Kupffer cells from resistant or sensitive mice to collaborate with immunocompetent lymphocytes. Our data suggest that Kupffer cells play a double role which is crucial in the pathogenesis of MHV 3-induced hepatitis. First, they act directly as the genetically determined sensitivity of mice to MHV 3 infection is correlated with the efficiency of the antiviral activity induced in Kupffer cells by LPS. Second, they act indirectly through the synthesis of different amounts of IL-1 induced by MHV 3. This hypothesis is further borne out by the effects of indomethacin treatment on the course of MHV 3 infection in A/J resistant mice in vivo.
Keller
F
F
Laboratoire de Virologie and INSERM U 74, Faculté de Médecine de Strasbourg, France.
Schmitt
C
C
Kirn
A
A
D000818:Animals; D002478:Cells, Cultured; D006524:Hepatitis, Viral, Animal / Q000209:etiology* / Q000276:immunology / Q000382:microbiology; D007375:Interleukin-1 / Q000096:biosynthesis; D007728:Kupffer Cells / Q000276:immunology / Q000382:microbiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D006517:Murine hepatitis virus / Q000276:immunology / Q000502:physiology*; D013045:Species Specificity; D014762:Viral Interference; D014779:Virus Replication
D007375:Interleukin-1; D008070:Lipopolysaccharides