Suppression of rat cytomegalovirus replication by antibodies against gamma interferon

Bart L. Haagmans, Peter H. Van Der Meide, Frans S. Stals, Alfons J.M. Van Den Eertwegh, Eric Claassen, Cathrien A. Bruggeman, Marian C. Horzinek, Virgil E.C.J. Schijns

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Abstract

The role of gamma interferon (IFN-γ) in the resolution of rat cytomegalovirus (RCMV) infection was investigated. In the spleen, IFN-γ- producing cells reached maximum numbers on day 7 after infection. Prophylactic treatment with high doses of recombinant rat IFN-γ exerted antiviral activity in fibroblasts and protected immunosuppressed rats against a lethal RCMV challenge. Remarkably, in immunocompetent rats, neutralization of endogenous IFN-γ 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-γ neutralizing antibodies. The observations were paralleled by in vitro findings: low concentrations of IFN-γ enhanced viral replication in both macrophages and fibroblasts. These data suggest that IFN-γ 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-γ.

Original languageEnglish
Pages (from-to)2305-2312
Number of pages8
JournalJournal of Virology
Volume68
Issue number4
DOIs
Publication statusPublished - Apr 1994

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