Blood, Vol. 94 No. 2 (July 15), 1999:
pp. 572-578
Interleukin-1 (IL-1) Inhibits Growth of Cytomegalovirus in Human Marrow
Stromal Cells: Inhibition Is Reversed Upon Removal of IL-1
Mineo Iwata,
Jeff Vieira,
Michael Byrne,
Heidi Horton, and
Beverly Torok-Storb
From the Clinical Research Division, Fred Hutchinson Cancer Research
Center, Seattle, WA; and Genetics Institute, Cambridge, MA.
A Toledo strain cytomegalovirus (CMV) containing the gene for green
fluorescent protein (GFP) under the control of elongation factor-1
promoter was used to study infection of human marrow stromal cells. Two
stromal cell lines were used: HS-5, which secretes copious amounts of
known cytokines and interleukins; and HS-27a, which does not secrete
these activities. CMV growth and spread was monitored by counting green
plaques and quantitating GFP intensity. Initial studies indicated that,
whereas HS-5 and 27a have similar susceptibilities to infection, as
evidenced by the same number of GFP+ cells at day 2, HS-5
appears more resistant to growth and spread of CMV. Furthermore,
conditioned media from HS-5 (HS-5 CM) inhibited CMV plaque formation in
HS-27a, suggesting that factors secreted by HS-5 are responsible for
limiting CMV growth. Neutralizing antibodies against interleukin-1
(IL-1) and IL-1
completely blocked the ability of HS-5 CM to
limit viral growth, suggesting that IL-1, which is known to be present
in HS-5 CM, is responsible for this effect. When exogenous IL-1 was
added to CMV-infected HS-27a, both the number of plaques and the
intensity of GFP was significantly reduced in IL-1-treated HS-27a
compared with untreated HS-27a (the number of plaques by day 18 was 20 ± 3 v 151 ± 12/well, respectively; GFP intensity was 535 ± 165 v 6,516 ± 652/well, respectively, in 4 separate
experiments). At day 21, when IL-1-treated, CMV-infected cultures
were passaged and then cultured in the absence of IL-1, CMV growth
progressed with the kinetics of the original untreated culture,
indicating that the IL-1 effect is reversible. Because HS-27a
expresses the type I IL-1 receptor, we speculate that the antiviral
effects are mediated through IL-1-induced changes in cellular gene
expression. DNA chip analysis of mRNA from IL-1-treated and
nontreated HS-27a cells has identified some candidate molecules.
