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A major role of macrophage activation by interferon-gamma during mouse hepatitis virus type 3 infection. I.
1Instituto Butantan, Laboratorio de Imunologia Viral, São Paulo, Brazil.
Abstract:
Resistance of mice to mouse hepatitis virus type 3 (MHV3) infection is genetically determined. Normal adult A/J mice are resistant, and BALB/c mice are susceptible. Higher titers of virus and interferon (IFN) in vivo were found in MHV3-infected BALB/c mice compared with A/J mice. In vitro activation of macrophages (M phi) by lipopolysaccharide (LPS) delayed MHV3 replication only in cells that originated from A/J mice, although cell populations from both A/J and BALB/c mice were able to synthesize comparable amounts of IFN-alpha/beta. Using specific antibodies, we have shown that the delayed MHV3 replication in LPS-activated A/J M phi was due, in part, to IFN-alpha/beta. A/J M phi were found to be more sensitive to IFN-gamma than to IFN-alpha/beta, and BALB/c M phi did not develop an antiviral state to either IFN. Cultured spleen cells from A/J mice synthesized more IFN-gamma than BALB/c spleen cells after specific or non-specific stimulation. The results indicate that IFN-activated M phi may play a crucial role in the resistance to MHV3 infection. Since IFN-gamma is produced in large amounts by A/J spleen cells after specific stimulation with MHV3 and is efficient in activating the A/J M phi, a T cell-dependent mechanism is likely to be involved.
Insights
Genetic resistance to mouse hepatitis virus type 3 (MHV3) involves interferon-gamma activated macrophages. A/J mice show resistance due to enhanced interferon-gamma production and macrophage sensitivity, suggesting a T cell-dependent mechanism.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Mouse hepatitis virus type 3 (MHV3) infection resistance is genetically controlled.
- A/J mice are resistant, while BALB/c mice are susceptible to MHV3.
- Susceptible BALB/c mice exhibit higher in vivo virus and interferon (IFN) titers post-infection.
Purpose of the Study:
- To investigate the role of macrophages and interferons in genetically determined MHV3 resistance.
- To elucidate the differential responses of A/J and BALB/c macrophages to MHV3 infection and IFN activation.
Main Methods:
- In vitro macrophage activation using lipopolysaccharide (LPS).
- Assessment of MHV3 replication in macrophages from resistant (A/J) and susceptible (BALB/c) mice.
- Quantification of IFN-alpha/beta and IFN-gamma synthesis and macrophage sensitivity to IFNs.
Main Results:
- LPS-activated macrophages from A/J mice showed delayed MHV3 replication, partly due to IFN-alpha/beta.
- A/J macrophages were more sensitive to IFN-gamma than IFN-alpha/beta.
- BALB/c macrophages did not develop an antiviral state to either IFN.
- A/J spleen cells produced more IFN-gamma upon stimulation compared to BALB/c.
Conclusions:
- Interferon-activated macrophages play a critical role in MHV3 resistance.
- Enhanced IFN-gamma production by A/J spleen cells and subsequent macrophage activation suggest a T cell-dependent mechanism in MHV3 resistance.