TY - JOUR
T1 - Interferon γ regulates acute and latent murine cytomegalovirus infection and chronic disease of the great vessels
AU - Presti, Rachel M.
AU - Pollock, Jessica L.
AU - Dal Canto, Albert J.
AU - O'Guin, Andrew K.
AU - Virgin IV, Herbert W.
PY - 1998/8/3
Y1 - 1998/8/3
N2 - To define immune mechanisms that regulate chronic and latent herpesvirus infection, we analyzed the role of interferon γ (IFN-γ) during murine cytomegalovirus (MCMV) infection. Lethality studies demonstrated a net protective role for IFN-γ independent of IFN-α/β, during acute MCMV infection. Mice lacking the IFN-γ receptor (IFN-γR(-/-)) 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-γ responses could lead to chronic vascular disease, we evaluated the role of IFN-γ, in MCMV latency. MCMV-infected IFN-γR(-/-) 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-γR was not required for establishment of latency. Using an in vitro explant reactivation model, we showed that IFN-γ reversibly inhibited MCMV reactivation from latency. This was at least partly explained by IFN-γ- mediated blockade of growth of low levels of MCMV in tissue explants. These in vivo and in vitro data suggest that IFN-γ 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-γ) 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.
AB - To define immune mechanisms that regulate chronic and latent herpesvirus infection, we analyzed the role of interferon γ (IFN-γ) during murine cytomegalovirus (MCMV) infection. Lethality studies demonstrated a net protective role for IFN-γ independent of IFN-α/β, during acute MCMV infection. Mice lacking the IFN-γ receptor (IFN-γR(-/-)) 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-γ responses could lead to chronic vascular disease, we evaluated the role of IFN-γ, in MCMV latency. MCMV-infected IFN-γR(-/-) 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-γR was not required for establishment of latency. Using an in vitro explant reactivation model, we showed that IFN-γ reversibly inhibited MCMV reactivation from latency. This was at least partly explained by IFN-γ- mediated blockade of growth of low levels of MCMV in tissue explants. These in vivo and in vitro data suggest that IFN-γ 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-γ) 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.
KW - Cytomegalovirus
KW - Interferon γ
KW - Latency
KW - Reactivation
KW - Vasculitis
UR - http://www.scopus.com/inward/record.url?scp=0032479923&partnerID=8YFLogxK
U2 - 10.1084/jem.188.3.577
DO - 10.1084/jem.188.3.577
M3 - Article
C2 - 9687534
AN - SCOPUS:0032479923
VL - 188
SP - 577
EP - 588
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 3
ER -