Tumor necrosis factor alpha promotes replication and pathogenicity of rat cytomegalovirus.
We investigated the role of tumor necrosis factor alpha (TNF-alpha) in the pathogenesis of rat cytomegalovirus (RCMV) infection. TNF-alpha levels found in the sera of radiation-immunosuppressed rats in the course of infection (> 350 pg/ml) correlated with the development of RCMV disease. Administration of anti-TNF-alpha antibodies strongly reduced the severity of pneumonia and led to a reduction in virus titers. In immunocompetent rats, anti-TNF-alpha antibodies also significantly suppressed viral replication. Conversely, administration of TNF-alpha augmented RCMV replication and aggravated the disease signs. In vitro, TNF-alpha enhanced RCMV replication in the macrophage, whereas a reduction of viral replication was observed in fibroblasts, indicating that the effect on viral replication is cell type specific. Besides activation of viral replication and exacerbation of RCMV disease, TNF-alpha also favored lymphoid and hematopoietic tissue reconstitution after irradiation, which may contribute to antiviral resistance and survival. This finding demonstrates the protean nature of TNF-alpha, with both beneficial and adverse effects for the host. Our results suggest that TNF-alpha plays an important role in modulating the pathogenesis of RCMV infection.
Haagmans
B L
BL
Department of Infectious Diseases and Immunology, Veterinary Faculty, University of Utrecht, The Netherlands.
Stals
F S
FS
van der Meide
P H
PH
Bruggeman
C A
CA
Horzinek
M C
MC
Schijns
V E
VE
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000628:therapy; D005347:Fibroblasts / Q000382:microbiology; D005720:Gamma Rays; D006410:Hematopoiesis / Q000187:drug effects; D007107:Immune System / Q000528:radiation effects; D007165:Immunosuppression Therapy; D016219:Immunotherapy, Adoptive; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha