Enhanced virus replication and inhibition of lymphocytic choriomeningitis virus disease in anti-gamma interferon-treated mice.
The role of gamma interferon (IFN-gamma) induced during a viral infection in the ability of the host to acquire antiviral immunity was studied in mice. They were injected subcutaneously daily with an ammonium sulfate-precipitated sheep anti-IFN-gamma antibody preparation able to neutralize 10(4) U of IFN-gamma. Specificity of the anti-IFN-gamma antiserum was demonstrated by absence of detectable activity against natural IFN-alpha and -beta. Controls were treated with a similarly prepared normal sheep serum. Treatment with the IFN-gamma-specific antibody preparation had no influence on the ability of mice to generate anti-vaccinia virus- or anti-vesicular stomatitis virus (VSV)-specific cytotoxic T-cell (CTL) responses or T helper-dependent immunoglobulin G responses to VSV. In contrast, treatment of mice with sheep anti-IFN-gamma impaired CTL responses against lymphocytic choriomeningitis (LCM) virus (LCMV, Aggressive isolate); in addition, under the experimental conditions used, it prevented lethal LCM. Cytotoxic T-cell activity measured in the spleens of anti-IFN-gamma-treated mice was comparable to that found in mice initially infected with a 100-fold-larger dose of LCMV. Evaluation of the effects of treatment on the kinetics of virus replication revealed that in both euthymic and athymic nude C57BL/6 mice, anti-IFN-gamma treatment led to an increase of virus titers up to 100-fold compared with control mice. Therefore, IFN-gamma may play a role in controlling viruses with tropism for lymphocytes and monocytes/macrophages, such as LCMV.
Leist
T P
TP
Institut für Pathologie, Universitätsspital, Zurich, Switzerland.
Eppler
M
M
Zinkernagel
R M
RM
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D005260:Female; D007106:Immune Sera / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007371:Interferon-gamma / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000382:microbiology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008819:Mice, Nude; D009500:Neutralization Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D014779:Virus Replication
D000914:Antibodies, Viral; D007106:Immune Sera; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007371:Interferon-gamma