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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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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