Suppression of rat cytomegalovirus replication by antibodies against gamma interferon.
The role of gamma interferon (IFN-gamma) in the resolution of rat cytomegalovirus (RCMV) infection was investigated. In the spleen, IFN-gamma-producing cells reached maximum numbers on day 7 after infection. Prophylactic treatment with high doses of recombinant rat IFN-gamma exerted antiviral activity in fibroblasts and protected immunosuppressed rats against a lethal RCMV challenge. Remarkably, in immunocompetent rats, neutralization of endogenous IFN-gamma activity significantly reduced the numbers of RCMV antigen-expressing cells in the spleen, the predominant site of viral replication. Moreover, protection of radiation-immunosuppressed infected rats by transferred immune T cells was enhanced by coinjection of IFN-gamma neutralizing antibodies. The observations were paralleled by in vitro findings: low concentrations of IFN-gamma enhanced viral replication in both macrophages and fibroblasts. These data suggest that IFN-gamma can play different and even opposite roles in the regulation of RCMV replication in vivo; T lymphocytes may contribute to the progression of RCMV infection by secreting IFN-gamma.
Haagmans
B L
BL
Department of Infectious Diseases and Immunology, Veterinary Faculty, Utrecht University, The Netherlands.
van der Meide
P H
PH
Stals
F S
FS
van den Eertwegh
A J
AJ
Claassen
E
E
Bruggeman
C A
CA
Horzinek
M C
MC
Schijns
V E
VE
D000818:Animals; D000911:Antibodies, Monoclonal; D003587:Cytomegalovirus / Q000254:growth & development*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005347:Fibroblasts / Q000382:microbiology; D007116:Immunization, Passive; D007165:Immunosuppression Therapy; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D007668:Kidney / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects
D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D007371:Interferon-gamma