Modulation of viral replication in macrophages persistently infected with the DA strain of Theiler's murine encephalomyelitis virus

<p>Abstract</p> <p>Background</p> <p>Demyelinating strains of Theiler's murine encephalomyelitis virus (TMEV) such as the DA strain are the causative agents of a persistent infection that induce a multiple sclerosis-like disease in the central nervous system of sus...

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Main Authors: Rombaut Bart, Merckx Ellen, Steurbaut Stephane, Vrijsen Raf
Format: Article
Language:English
Published: BMC 2008-08-01
Series:Virology Journal
Online Access:http://www.virologyj.com/content/5/1/89
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spelling doaj-af8e0977382f45b7ba1a9d6e9d16c8f92020-11-25T02:49:15ZengBMCVirology Journal1743-422X2008-08-01518910.1186/1743-422X-5-89Modulation of viral replication in macrophages persistently infected with the DA strain of Theiler's murine encephalomyelitis virusRombaut BartMerckx EllenSteurbaut StephaneVrijsen Raf<p>Abstract</p> <p>Background</p> <p>Demyelinating strains of Theiler's murine encephalomyelitis virus (TMEV) such as the DA strain are the causative agents of a persistent infection that induce a multiple sclerosis-like disease in the central nervous system of susceptible mice. Viral persistence, mainly associated with macrophages, is considered to be an important disease determinant that leads to chronic inflammation, demyelination and autoimmunity. In a previous study, we described the establishment of a persistent DA infection in RAW macrophages, which were therefore named DRAW.</p> <p>Results</p> <p>In the present study we explored the potential of diverse compounds to modulate viral persistence in these DRAW cells. Hemin was found to increase viral yields and to induce cell lysis. Enviroxime and neutralizing anti-TMEV monoclonal antibody were shown to decrease viral yields, whereas interferon-α and interferon-γ completely cleared the persistent infection. We also compared the cytokine pattern secreted by uninfected RAW, DRAW and interferon-cured DRAW macrophages using a cytokine protein array. The chemokine RANTES was markedly upregulated in DRAW cells and restored to a normal expression level after abrogation of the persistent infection with interferon-α or interferon-γ. On the other hand, the chemokine MCP-1 was upregulated in the interferon-cured DRAW cells.</p> <p>Conclusion</p> <p>We have identified several compounds that modulate viral replication in an <it>in vitro </it>model system for TMEV persistence. These compounds now await further testing in an <it>in vivo </it>setting to address fundamental questions regarding persistent viral infection and immunopathogenesis.</p> http://www.virologyj.com/content/5/1/89
collection DOAJ
language English
format Article
sources DOAJ
author Rombaut Bart
Merckx Ellen
Steurbaut Stephane
Vrijsen Raf
spellingShingle Rombaut Bart
Merckx Ellen
Steurbaut Stephane
Vrijsen Raf
Modulation of viral replication in macrophages persistently infected with the DA strain of Theiler's murine encephalomyelitis virus
Virology Journal
author_facet Rombaut Bart
Merckx Ellen
Steurbaut Stephane
Vrijsen Raf
author_sort Rombaut Bart
title Modulation of viral replication in macrophages persistently infected with the DA strain of Theiler's murine encephalomyelitis virus
title_short Modulation of viral replication in macrophages persistently infected with the DA strain of Theiler's murine encephalomyelitis virus
title_full Modulation of viral replication in macrophages persistently infected with the DA strain of Theiler's murine encephalomyelitis virus
title_fullStr Modulation of viral replication in macrophages persistently infected with the DA strain of Theiler's murine encephalomyelitis virus
title_full_unstemmed Modulation of viral replication in macrophages persistently infected with the DA strain of Theiler's murine encephalomyelitis virus
title_sort modulation of viral replication in macrophages persistently infected with the da strain of theiler's murine encephalomyelitis virus
publisher BMC
series Virology Journal
issn 1743-422X
publishDate 2008-08-01
description <p>Abstract</p> <p>Background</p> <p>Demyelinating strains of Theiler's murine encephalomyelitis virus (TMEV) such as the DA strain are the causative agents of a persistent infection that induce a multiple sclerosis-like disease in the central nervous system of susceptible mice. Viral persistence, mainly associated with macrophages, is considered to be an important disease determinant that leads to chronic inflammation, demyelination and autoimmunity. In a previous study, we described the establishment of a persistent DA infection in RAW macrophages, which were therefore named DRAW.</p> <p>Results</p> <p>In the present study we explored the potential of diverse compounds to modulate viral persistence in these DRAW cells. Hemin was found to increase viral yields and to induce cell lysis. Enviroxime and neutralizing anti-TMEV monoclonal antibody were shown to decrease viral yields, whereas interferon-α and interferon-γ completely cleared the persistent infection. We also compared the cytokine pattern secreted by uninfected RAW, DRAW and interferon-cured DRAW macrophages using a cytokine protein array. The chemokine RANTES was markedly upregulated in DRAW cells and restored to a normal expression level after abrogation of the persistent infection with interferon-α or interferon-γ. On the other hand, the chemokine MCP-1 was upregulated in the interferon-cured DRAW cells.</p> <p>Conclusion</p> <p>We have identified several compounds that modulate viral replication in an <it>in vitro </it>model system for TMEV persistence. These compounds now await further testing in an <it>in vivo </it>setting to address fundamental questions regarding persistent viral infection and immunopathogenesis.</p>
url http://www.virologyj.com/content/5/1/89
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