Interleukin-1-mediated inhibition of cytomegalovirus replication is due to increased IFN-beta production.
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.
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. jhabecke@fhcrc.org
Julie
J
Randolph-Habecker
Mineo
M
Iwata
Adam P
AP
Geballe
Sohail
S
Jarrahian
Beverly
B
Torok-Storb
D000998:Antiviral Agents / Q000494:pharmacology*; D001853:Bone Marrow / Q000821:virology; D003587:Cytomegalovirus / Q000502:physiology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D007375:Interleukin-1 / Q000235:genetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D007375:Interleukin-1; D011994:Recombinant Proteins; D016899:Interferon-beta