A major role of macrophage activation by interferon-gamma during mouse hepatitis virus type 3 infection. I. Genetically dependent resistance.
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.
Lucchiari
M A
MA
Instituto Butantan, Laboratorio de Imunologia Viral, São Paulo, Brazil.
Pereira
C A
CA
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D006524:Hepatitis, Viral, Animal / Q000235:genetics* / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D007371:Interferon-gamma / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D006517:Murine hepatitis virus / Q000235:genetics / Q000254:growth & development; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D000914:Antibodies, Viral; D008070:Lipopolysaccharides; D003208:Concanavalin A; D007371:Interferon-gamma