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. 1994 Apr;68(4):2297–2304. doi: 10.1128/jvi.68.4.2297-2304.1994

Tumor necrosis factor alpha promotes replication and pathogenicity of rat cytomegalovirus.

B L Haagmans 1, F S Stals 1, P H van der Meide 1, C A Bruggeman 1, M C Horzinek 1, V E Schijns 1
PMCID: PMC236705  PMID: 8139014

Abstract

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.

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Selected References

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