Skip to main content
NCBI home page
Wiley - PMC COVID-19 Collection logoLink to Wiley - PMC COVID-19 Collection
. 2006 Mar 27;47(2):87–96. doi: 10.1111/j.1574-6968.1988.tb02496.x

Interaction of mouse hepatitis virus 3 with Kupffer cells explanted from susceptible and resistant mouse strains. Antiviral activity, interleukin‐1 synthesis

F Keller 1,✉, C Schmitt 1, A Kirn 1
PMCID: PMC7110325  PMID: 2856206

Abstract

Abstract 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‐proceesing function of the Kupffer cellsof 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.

Keywords: Mouse hepatitis virus 3, Kupffer cell, Antiviral property, IL‐1 synthesis

REFERENCES

  • [1]. Levy‐Leblond, E. , Oth, D. and Dupuy, J.M. (1979) Genetic study of mouse sensitivity to MHV 3 infection: influence of the H‐2 complex J. Immunol., 122, 1359–1362. [PubMed] [Google Scholar]
  • [2]. Arnheiter, H. , Thomas, B. and Haller, O. (1982) Adult mouse hepatocytes in primary monolayer culture express genetic resistance to mouse hepatitis virus type 3 J. Immunol., 129, 1275–1281. [PubMed] [Google Scholar]
  • [3]. Virelizier, J.L. and Allison, A.C. (1976) Correlation of persistent mouse hepatitis virus (MHV 3) infection with its effect on mouse macrophage cultures Arch. Virol., 50, 279–285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [4]. Pereira, C.A. , Steffan, A.M. and Kirn, A. (1984) Interaction between mouse hepatitis viruses and primary cultures of Kupffer and endothelial liver cells from resistant and susceptible inbred mouse strains J. Gen. Virol., 65, 1617–1619. [DOI] [PubMed] [Google Scholar]
  • [5]. Levy, G.A. , Leibowitz, J.L. and Edgington, T.S. (1981) Induction of monocyte procoagulant activity by murine hepatitis virus type 3 parallels disease susceptibility in mice J. Exp. Med., 154, 1150–1163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [6]. McPhee, P.J. , Dindzans, V.J. , Fung, L.S. and Levy, G.A. (1985) Acute and chronic changes in the microcirculation of the liver in inbred strains of mice following infection with mouse hepatitis virus type 3 Hepatology, 5, 649–660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [7]. Pereira, C.A. , Steffan, A.M. and Kirn, A. (1984) Kupffer and endothelial liver cell damage renders A/J mice susceptible to mouse hepatitis virus type 3 Virus Res., 1, 557–563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [8]. Pereira, C.A. , Mercier, G. , Oth, D. and Dupuy, J.M. (1984) Induction of natural killer cells and interferon during mouse hepatitis virus infection of resistant and susceptible inbred mouse strains Immunobiology, 166, 35–44. [DOI] [PubMed] [Google Scholar]
  • [9]. Kirn, A. , Steffan, A.M. and Bingen, A. (1980) Inhibition of erythrophagocytosis by cultured rat Kupffer cells infected with frog virus 3 J. Reticuloendothel. Soc.s, 28, 381–389. [PubMed] [Google Scholar]
  • [10]. Keller, F. , Wild, M.T. and Kirn, A. (1985) In vitro antiviral properties of endotoxin‐activated rat Kupffer cells J. Leukocyte Biol., 38, 293. [DOI] [PubMed] [Google Scholar]
  • [11]. Gearing, J.H.A. , Johnstone, A.P. and Thorpe, R. (1985) Production and assay of interleukins J. Immunol. Methods, 83, 1–27. [DOI] [PubMed] [Google Scholar]
  • [12]. Rogoff, T.M. and Lipsky, P.E. (1980) Antigen presentation by isolated guinea pig Kupffer cells J. Imm., 124, 1740–1744. [PubMed] [Google Scholar]
  • [13]. Keller, F. , Pereira, C.A. , Wild, M.T. , Koehren, F. and Kirn, A. (1986) In Kupffer cells activated in vitro display antiviral properties, in cells of the hepatic sinusoid (Kirn A., Knook D.L. and Wisse E., Eds) pp 363–364 The Kupffer Cell Foundation, Rijswijk . [Google Scholar]
  • [14]. Pereira, C.A. , Steffan, A.M. , Klein, F. , Rebel, G. and Kirn, A. (1986) Kupffer cells (KC) from mice fed a hypercholesterolemic diet (HC) have lost their ability to be activated by endotoxin in vitro In Cells of the Hepatic Sinusoid (Kirn A., Knook D.L. and Wisse E., Eds) pp 365–370 The Kupffer Cell Foundation, Rijswijk . [Google Scholar]
  • [15]. MacNaughton, M.R. and Patterson, S. (1980) Mouse hepatitis virus strain 3 infection of C57, A/Sn and A/J strain mice and their macrophages Arch. Virol., 66, 71–75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [16]. Dinarello, C.A. (1984) Interleukin‐1 Rev. Inf. Dis., 6, 51–95. [DOI] [PubMed] [Google Scholar]
  • [17]. Roberts, N.J. Jr. , Prill, A.H. and Mann, T.M. (1986) Interleukin I and interleukin I inhibitor production by human macrophages exposed to influenza virus or respiratory syncitial virus J. Exp. Med., 163, 511–519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [18]. Bevilacqua, M.P. , Pober, J.S. , Wheeler, M.E. , Cotran, R.S. and Gimbrone, M.A. (1985) Interleukin‐1 activation of vascular endothelium. Effects on procoagulant activity and leukocyte adhesion Am. J. Pathol., 121, 394–403. [PMC free article] [PubMed] [Google Scholar]
  • [19]. Bevilacqua, M.P. , Pober, J.S. , Wheeler, M.E. , Cotran, R.S. and Gimbrone, M.A. (1985) Interleukin‐1 acts on cultured human vascular endothelium to increase the adhenion of polymorphonuclear leukocytes, monocytes and related leukocyte cell lines J. Clin. Invest., 76, 2003–2011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [20]. Abecassis, M. , Falk, J. , Dindzans, V. , Lopatin, W. , Makowa, L. , Levy, G. and Falk, R. (1987) Prostaglandin E2 prevents fulminant hepatitis and the induction of procoagulant activity in susceptible animals Transplant. Proc., 19, 1103–1105. [PubMed] [Google Scholar]
  • [21]. Le Prevost, C. , Levy‐Leblond, E. , Virelizier, J.L. and Dupuy, J.M. (1975) Immunopathology of mouse hepatitis virus type 3 infection. I. Role of humoral and cell‐mediated immunity in resistance mechanisms J. Immunol., 114, 221–225. [PubMed] [Google Scholar]
  • [22]. Dupuy, J.M. , Levy‐Leblond, E. and Le Prevost, C. (1975) Immunopathology of mouse hepatitis virus type 3 infection. II. Effect of immunosuppression in resistant mice J. Immunol., 114, 226–230. [PubMed] [Google Scholar]
  • [23]. Le Prevost, C. , Virelizier, J.L. and Dupuy, J.M. (1975) Immunopathology of mouse hepatitis virus type 3 infection. III. Clinical and virologic observation of a persistent viral infection J. Immunol., 115, 640–643. [PubMed] [Google Scholar]

Articles from FEMS Microbiology Letters are provided here courtesy of Wiley

RESOURCES