In vivo depletion of interferon-gamma leads to susceptibility of A/J mice to mouse hepatitis virus 3 infection

Abstract

The possible role of interferon-gamma (IFN-y) in the resistance of A/J mice to MHV3 infection was investigated. Monoclonal antibodies specific for IFN-y, CD4 and CDS molecules were administered in vivo to deplete selectively the IFN -y synthesized or the appropriate subset of T cells. The animals were then infected with MHV3 and the course of infection was followed by studying different parameters, such as, the mortality, the virus growth in the tissues and the IFN-y synthesis in sera and peritoneal exudates. After MHV3 infection, a full resistance of control A/J mice was observed, in contrast to the high mortality rate observed among the depleted animals, where higher virus titers were found in different tissues. The IFN-y synthesis in sera and peritoneal exudates of depleted mice, after MHV3 infection, drastically decreased when compared to that detected in control mice. The data presented are consistent with the hypothesis that IFN-y plays an essential role in the resistance of A/J mice to MHV3 infection.

The novel CD4+CD25+ regulatory T cell effector molecule fibrinogen-like protein 2 contributes to the outcome of murine fulminant viral hepatitis

“…Both interferon gamma and tumor necrosis factor can induce fgl2 linking these observations to the pathogenesis of MHV-3. 21,35,36 The results of this study clearly demonstrate that FGL2 is an important effector cytokine of Tregs that contributes to host susceptibility to MHV3-induced FH. Because we have shown that patients with FH and chronic HBV and hepatitis C virus infection have increased levels of FGL2, 30,37 the data presented here in concert with human studies suggest that measurement of FGL2 levels in the plasma may be useful in predicting the outcome of both experimental and human viral hepatitis and may provide a rationale for targeting FGL2 for the treatment of patients with acute and chronic viral hepatitis.…”

Preferential Replication of Vaccinia Virus in the Ovaries is Independent of Immune Regulation Through IL-10 and TGF-β

“…Its functionality actually varies with the type and conditions of infection. Mice with a disrupted gene for IFN-cR1 or IFN-c, or mice treated with anti-IFN-c, are more susceptible to ectromelia virus, CMV, and mouse hepatitis virus infection (39)(40)(41)(42)(43), due to the loss of direct antiviral activity via IFN-c. In contrast, IFN-c plays a redundant role in controlling acute infection with vesicular stomatitis virus, pseudorabies virus, c-herpesvirus, and influenza virus (39,43,44).…”

A 2',5'-oligoadenylate analogue inhibits murine hepatitis virus strain 3 (MHV-3) replication in vitro but does not reduce MHV-3-related mortality or induction of procoagulant activity in susceptible mice

“…Unlike adult A/J mice, A/J mice less than 4 weeks old are fully susceptible to MHV-3 with susceptibility correlating with the inability of these mice to produce IFN-y in vivo in response to MHV-3 (Lucchiari & Pereira, 1990). In mice resistant and semiresistant to MHV-3, treatment with MAbs raised against IFN results in conversion from resistance to susceptibility (Lucchiari et al, 1992;Virdizier & Gresser, 1978). Treatment with IFN type 1 has been shown to prolong survival following MHV exposure, particularly when treatment is started prior to viral infection (Minagawa et al, 1987;Kato et al, 1986).…”

“…T lymphocytes have been established as being important in the development of resistance to MHV infection (Le Prevost et al, 1975;Woodward et al, 1984;Lucchiari et al, 1992). In vivo studies of mice infected with MHV-JHM, a strain of virus closely related to MHV-3, have demonstrated that resistance could be conferred by adoptive transfer of virus-specific Lyt-1 +2-, L3T4 ÷ T cell clones (Stohlman et al, 1986).…”

“…Previous studies have demonstrated a crucial role for interferons (IFNs) in resistance to MHV-3 infection (Lucchiari & Pereira, 1989, 1990Lucchiari et al, 1991Lucchiari et al, , 1992Virelizier & Gressor, 1978). These cytokines produce direct antiviral effects as well as effects on the immune response of the host which result in decreased viral infectivity and cellular injury (Whitaker-Dowling & Youngner, 1987;Borden, 1992;Grossberg, 1987;Staeheli, 1990;Samuel, 1987;Pestka et al, 1987).…”