Interleukin-1-Mediated Inhibition of Cytomegalovirus Replication Is Due to Increased IFN- β Production

Abstract

Previous studies have demonstrated that the intercellular spread of cytomegalovirus (CMV) is reduced in marrow stromal cells that either secrete interleukin-1 (IL-1) or are treated with exogenous IL-1. Here, we report that IL-1-treated marrow stromal cells and fibroblasts, when infected with CMV, produce decreased amounts of infectious progeny virus. CMV-infected cells treated with IL-1 contained more interferon-β (IFN-β) mRNA at 24 h postinfection compared with untreated, infected cells. IFN-β protein secreted into fibroblast culture supernatants increased from 46± 1 IU/ml in untreated, infected cells to 116 ± 5 IU/ml in IL-1-treated infected cells. When IFN-β activity was inhibited, using blocking antibodies to either the cytokine or the IFN-α/β receptor, the addition of IL-1 no longer limited viral spread. Furthermore, viral spread in nonIL-1-treated cultures was inhibited by the addition of recombinant IFN-β. These studies suggest that IL-1 functions to limit CMV spread by increasing the expression of IFN-β, which in turn reduces production of infectious virus.