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Interferon γ Regulates Acute and Latent Murine Cytomegalovirus Infection and Chronic Disease of the Great Vessels

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 l...

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Autores principales: Presti, Rachel M., Pollock, Jessica L., Dal Canto, Albert J., O'Guin, Andrew K., Virgin IV, Herbert W.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1998
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212470/
https://www.ncbi.nlm.nih.gov/pubmed/9687534
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author Presti, Rachel M.
Pollock, Jessica L.
Dal Canto, Albert J.
O'Guin, Andrew K.
Virgin IV, Herbert W.
author_facet Presti, Rachel M.
Pollock, Jessica L.
Dal Canto, Albert J.
O'Guin, Andrew K.
Virgin IV, Herbert W.
author_sort Presti, Rachel M.
collection PubMed
description 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.
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spelling pubmed-22124702008-04-16 Interferon γ Regulates Acute and Latent Murine Cytomegalovirus Infection and Chronic Disease of the Great Vessels Presti, Rachel M. Pollock, Jessica L. Dal Canto, Albert J. O'Guin, Andrew K. Virgin IV, Herbert W. J Exp Med Articles 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. The Rockefeller University Press 1998-08-03 /pmc/articles/PMC2212470/ /pubmed/9687534 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Presti, Rachel M.
Pollock, Jessica L.
Dal Canto, Albert J.
O'Guin, Andrew K.
Virgin IV, Herbert W.
Interferon γ Regulates Acute and Latent Murine Cytomegalovirus Infection and Chronic Disease of the Great Vessels
title Interferon γ Regulates Acute and Latent Murine Cytomegalovirus Infection and Chronic Disease of the Great Vessels
title_full Interferon γ Regulates Acute and Latent Murine Cytomegalovirus Infection and Chronic Disease of the Great Vessels
title_fullStr Interferon γ Regulates Acute and Latent Murine Cytomegalovirus Infection and Chronic Disease of the Great Vessels
title_full_unstemmed Interferon γ Regulates Acute and Latent Murine Cytomegalovirus Infection and Chronic Disease of the Great Vessels
title_short Interferon γ Regulates Acute and Latent Murine Cytomegalovirus Infection and Chronic Disease of the Great Vessels
title_sort interferon γ regulates acute and latent murine cytomegalovirus infection and chronic disease of the great vessels
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212470/
https://www.ncbi.nlm.nih.gov/pubmed/9687534
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