The virulence of mouse hepatitis virus 3, as evidenced by permissivity of cultured hepatic cells toward escape mutants

Martín, J. P.; Chen, W.; Koehren, F.; Pereira, Carlos Augusto

doi:10.1016/s0923-2516(07)80034-3

Cited by 15 publications

(37 citation statements)

References 12 publications

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“…Infections with attenuated variants of MHV3, however, induced higher levels of immunosuppressive cytokines or delayed production of the latter. It has been demonstrated previously that the attenuation levels of virus variants reflect their inability to infect LSEC (51·6-MHV3) or LSEC and KC (CL12-MHV3) [25], suggesting that their mild virulent phenotype may depend upon the integrity of LSEC and KC cells and their role in the control of liver inflammation through the production of immunosuppressive cytokines. In addition, the lower disturbance in immunosuppressive cytokines induced by the higher attenuated CL12-MHV3 variant when compared with the low attenuated 51·6-MHV3 variant indicates that the integrity of KC cells is more important than that of LSEC in the control of inflammatory responses during acute viral hepatitis.…”

Section: Cell Populations Viral Infection † Times Post-infection (H)mentioning

confidence: 96%

“…The 51·6-MHV3 variant is less virulent than L2-MHV3, killing mice within 5-9 days, inducing moderate liver necrosis and infecting KC cells, but not LSEC [25]. The highly attenuated CL12-MHV3 variant induces the death of mice within 8-10 days, minor hepatitis with perivascular inflammatory foci, no immunodeficiency and undetectable infectious virions in LSEC or KC [25]. However, viral replication in liver was similar for pathogenic parental virus and attenuated variants [26], suggesting that the gravity of hepatitis depends on the intensity of the inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

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Intrahepatic endothelial and Kupffer cells involved in immunosuppressive cytokines and natural killer (NK)/NK T cell disorders in viral acute hepatitis

Jacques

Bleau

Martín

et al. 2008

Clinical and Experimental Immunology

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Section: Cell Populations Viral Infection † Times Post-infection (H)mentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Intrahepatic endothelial and Kupffer cells involved in immunosuppressive cytokines and natural killer (NK)/NK T cell disorders in viral acute hepatitis

Jacques

Bleau

Martín

et al. 2008

Clinical and Experimental Immunology

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“…[10][11][12] Histopathological studies revealed an extensive necrosis with inflammatory perivascular foci and impairment of immunosuppressive cytokines such as IL-4, IL-10, prostaglandin E 2 (PGE 2 ) and transforming growth factor (TGF)-b. 13,14 Carcinoembryonic antigen cell adhesion molecules 1 (CEACAM1), previously known as biliary glycoproteins, are members of the immunoglobulin superfamily. 15 Murine CEACAM1 proteins are mostly present in the liver and intestine and have been reported to act as receptors for different bacterial and viral pathogens, including MHV.…”

Section: Introductionmentioning

confidence: 99%

Macrophage interleukin‐6 and tumour necrosis factor‐α are induced by coronavirus fixation to Toll‐like receptor 2/heparan sulphate receptors but not carcinoembryonic cell adhesion antigen 1a

et al. 2009

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A rapid antiviral immune response may be related to viral interaction with the host cell leading to activation of macrophages via pattern recognition receptors (PPRs) or specific viral receptors. Carcinoembryonic cell adhesion antigen 1a (CEACAM1a) is the specific receptor for the mouse hepatitis virus (MHV), a coronavirus known to induce acute viral hepatitis in mice. The objective of this study was to understand the mechanisms responsible for the secretion of high-pathogenic MHV3-induced inflammatory cytokines. We report that the induction of the pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha in peritoneal macrophages does not depend on CEACAM1a, as demonstrated in cells isolated from Ceacam1a(-/-) mice. The induction of IL-6 and TNF-alpha production was related rather to the fixation of the spike (S) protein of MHV3 on Toll-like receptor 2 (TLR2) in regions enriched in heparan sulphate and did not rely on viral replication, as demonstrated with denatured S protein and UV-inactivated virus. High levels of IL-6 and TNF-alpha were produced in livers from infected C57BL/6 mice but not in livers from Tlr2(-/-) mice. The histopathological observations were correlated with the levels of those inflammatory cytokines. Depending on mouse strain, the viral fixation to heparan sulfate/TLR2 stimulated differently the p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB in the induction of IL-6 and TNF-alpha. These results suggest that TLR2 and heparan sulphate receptors can act as new viral PPRs involved in inflammatory responses.

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“…It has been proposed that an autocrine loop initiated by an interaction beween lymphocytes and Kupffer cells can cause CD4 ϩ activation and IFN-␥ production, which in turn may induce NO release by Kupffer cells to suppress T cell proliferation (23,24). Kupffer cells are an important target for pathogenic L2-MHV3 replication in the liver (25,26), suggesting that this proposed mechanism would be altered during viral infection. YAC-MHV3 replication was lower in macrophages than that produced by pathogenic L2-MHV3 infection (27), suggesting that the tolerance, which is under control by Kupffer cells, would not be disturbed in YAC-MHV3-infected mice.…”

mentioning

confidence: 99%

“…In addition, the number of leucocytes adhering to intrahepatic EC is controlled by a leucocyte-EC interactions and remains constant even if the total number or circulating leukocytes varies over time (30). However, EC are an important target for pathogenic L2-MHV3 replication but not for attenuated viral strains (25,26). Other cytokines, such as IL-10 and prostanoids released by Kupffer cells, downregulate leukocyte adhesion to intrahepatic EC by decreasing surface expression of CD54 and CD116 (29) and then avoiding the recruitment of lymphoid cells and the immune-mediated liver damage by antigens from portal venous blood (31,32).…”

mentioning

confidence: 99%

Recovery from Mouse Hepatitis Virus Infection Depends on Recruitment of CD8+ Cells Rather Than Activation of Intrahepatic CD4+αβ−TCRinter or NK-T Cells

Lamontagne

Lusignan

Page

2001

Clinical Immunology

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Mouse hepatitis virus (MHV) provides an excellent animal model for the study of the immunopathological mechanisms involved in hepatic viral diseases. We previously generated an attenuated viral variant, YAC-MHV3, which induces a subclinical disease and recovery within 15 days. In contrast, the L2-MHV3 strain induces the development of a fulminant hepatitis, leading to death within 3 days. In this paper, we document intrahepatic and splenic T cell subpopulations involved in the hepatitis process and viral elimination identified in attenuated or pathogenic MHV3-infected C57BL/6 mice. Percentages of intrahepatic CD4(+) cells decreased in attenuated YAC-MHV3-infected mice, while they increased in mice infected with pathogenic L2-MHV3, compared with uninfected animals. Moreover, in YAC-MHV3-infected mice, the percentages of intrahepatic CD8(+) cells slightly decreased at 24 h pi, then increased until 15 days pi. In contrast, the CD4/CD8 ratios of splenic lymphoid subpopulations increased in the first days of infection and returned to normal values at 15 days pi. Intrahepatic NK1.1(+)alphabeta - TCR(inter) cells decreased in both virally infected groups of mice, while CD4(+)alphabeta - TCR(inter) LFA-1(high) cells increased in L2-MHV3-infected mice, in contrast with what was seen in YAC-MHV3-infected mice. However, these cells became anergic following Con A or PHA stimulation. Ex vivo studies showed that only the intrahepatic CD8(+) cells that were increased in YAC-MHV3-infected mice could be stimulated by lectins. In addition, in vitro viral infections revealed that L2-MHV3 viral infection led to an increase of intrahepatic CD4(+)alphabeta - TCR(inter) cells in the absence of CD8(+) cells only. These results indicate that the attenuated phenotype of the YAC-MHV3 virus is related to two different mechanisms: the first involves no increase of intrahepatic CD4(+)alphabeta - TCR(inter) or NK-T cells, while the second favors the recruitment and activation of CD8(+) cells in liver. The results are discussed in relation to the integrity of intrahepatic immune tolerance mechanisms and immune-mediated viral elimination.

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The virulence of mouse hepatitis virus 3, as evidenced by permissivity of cultured hepatic cells toward escape mutants

Cited by 15 publications

References 12 publications

Intrahepatic endothelial and Kupffer cells involved in immunosuppressive cytokines and natural killer (NK)/NK T cell disorders in viral acute hepatitis

Intrahepatic endothelial and Kupffer cells involved in immunosuppressive cytokines and natural killer (NK)/NK T cell disorders in viral acute hepatitis

Macrophage interleukin‐6 and tumour necrosis factor‐α are induced by coronavirus fixation to Toll‐like receptor 2/heparan sulphate receptors but not carcinoembryonic cell adhesion antigen 1a

Recovery from Mouse Hepatitis Virus Infection Depends on Recruitment of CD8+ Cells Rather Than Activation of Intrahepatic CD4+αβ−TCRinter or NK-T Cells

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