Tumor necrosis factor alpha promotes replication and pathogenicity of rat cytomegalovirus

Bart L. Haagmans, Frans S. Stals, Peter H. Van Der Meide, Cathrien A. Bruggeman, Marian C. Horzinek, Virgil E.C.J. Schijns*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

40 Citations (Scopus)

Abstract

We investigated the role of tumor necrosis factor alpha (TNF-α) in the pathogenesis of rat cytomegalovirus (RCMV) infection. TNF-α 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-α antibodies strongly reduced the severity of pneumonia and led to a reduction in virus titers. In immunocompetent rats, anti-TNF-α antibodies also significantly suppressed viral replication. Conversely, administration of TNF-α augmented RCMV replication and aggravated the disease signs. In vitro, TNF-α 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-α 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-α, with both beneficial and adverse effects for the host. Our results suggest that TNF-α plays an important role in modulating the pathogenesis of RCMV infection.

Original languageEnglish
Pages (from-to)2297-2304
Number of pages8
JournalJournal of Virology
Volume68
Issue number4
DOIs
Publication statusPublished - 1 Apr 1994
Externally publishedYes

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