Interleukin-1-mediated inhibition of cytomegalovirus replication is due to increased IFN-beta production

J Interferon Cytokine Res. 2002 Jul;22(7):765-72. doi: 10.1089/107999002320271350.

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-beta (IFN-beta) mRNA at 24 h postinfection compared with untreated, infected cells. IFN-beta 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-beta activity was inhibited, using blocking antibodies to either the cytokine or the IFN-alpha/beta 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-beta. These studies suggest that IL-1 functions to limit CMV spread by increasing the expression of IFN-beta, which in turn reduces production of infectious virus.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Bone Marrow / virology
  • Cytomegalovirus / physiology*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / virology
  • Humans
  • Interferon-beta / biosynthesis*
  • Interferon-beta / genetics
  • Interferon-beta / physiology
  • Interleukin-1 / genetics
  • Interleukin-1 / pharmacology*
  • Recombinant Proteins / pharmacology
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Stromal Cells / virology
  • Virus Replication / drug effects*

Substances

  • Antiviral Agents
  • Interleukin-1
  • Recombinant Proteins
  • Interferon-beta