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J. Exp. Med.,
Volume 188, Number 3, August 3, 1998 577-588
Regulates Acute and Latent Murine
Cytomegalovirus Infection and Chronic Disease of the
Great Vessels
By
From the Center for Immunology, Departments of Pathology and Molecular Microbiology, Washington
University School of Medicine, St. Louis, Missouri 63110
To define immune mechanisms that regulate chronic and latent herpesvirus infection, we analyzed the role of interferon 
(IFN-) during murine cytomegalovirus (MCMV) infection. Lethality studies demonstrated a net protective role for IFN-, independent of IFN-
/
, during
acute MCMV infection. Mice lacking the IFN- receptor (IFN-R
/) developed and maintained striking chronic aortic inflammation. Arteritis was associated with inclusion bodies and
MCMV antigen in the aortic media. To understand how lack of IFN- responses could lead to
chronic vascular disease, we evaluated the role of IFN- in MCMV latency. MCMV-infected
IFN-R/ mice shed preformed infectious MCMV in spleen, peritoneal exudate cells, and
salivary gland for up to 6 mo after infection, whereas the majority of congenic control animals
cleared chronic productive infection. However, the IFN-R was not required for establishment of latency. Using an in vitro explant reactivation model, we showed that IFN- reversibly inhibited MCMV reactivation from latency. This was at least partly explained by IFN--
mediated blockade of growth of low levels of MCMV in tissue explants. These in vivo and in
vitro data suggest that IFN- regulation of reactivation from latency contributes to control of
chronic vascular disease caused by MCMV. These studies are the first to demonstrate that a
component of the immune system (IFN-) is necessary to regulate MCMV-associated elastic
arteritis and latency in vivo and reactivation of a herpesvirus from latency in vitro. This provides a new model for analysis of the interrelationships among herpesvirus latency, the immune
system, and chronic disease of the great vessels.
;
latency;
reactivation;
cytomegalovirus;
vasculitis
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