The Leader Protein of Theiler's Virus Inhibits Immediate-Early Alpha/Beta Interferon Production

Pesch, Vincent Van; Eyll, Olivier van; Michiels, Thomas

doi:10.1128/jvi.75.17.7811-7817.2001

Cited by 115 publications

(155 citation statements)

References 38 publications

(24 reference statements)

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“…Viruses and Cell Culture-Viruses used in this study were Theiler's virus DA1 and its L cys mutant, TM598, carrying two Cys to Arg mutations, disrupting the zinc finger of the L protein (29,30). The KJ6 and TM659 are the corresponding wild-type and L cys -mutant viruses carrying a capsid adapted to infect L929 cells (29,31).…”

Section: Methodsmentioning

confidence: 99%

“…The KJ6 and TM659 are the corresponding wild-type and L cys -mutant viruses carrying a capsid adapted to infect L929 cells (29,31). These viruses were produced as described previously by transfection of BHK-21 cells with viral RNAs transcribed in vitro from the corresponding infectious cDNA clones, pTMDA1, pTM598, pKJ6, and pTM659 (29).…”

Section: Methodsmentioning

confidence: 99%

“…Viruses were titrated on BHK-21 cells by a standard plaque assay. BHK-21, COS-7, BALB/3T3, and L929 cells were cultured as described previously (29).…”

Section: Methodsmentioning

confidence: 99%

“…We have previously shown that in murine fibroblasts infected with Theiler's murine encephalomyelitis virus (TMEV or Theiler's virus), IFN-␣ was transcribed despite the inhibition of the immediate-early IFN production by the leader peptide en-□ S The on-line version of this article (available at http://www.jbc.org) coded by this virus (29). This result suggested that contrary to the predictions of the model, certain IFN-␣ subtype genes could be transcribed independently of the autocrine or paracrine loop mediated by the immediate-early IFNs.…”

mentioning

confidence: 99%

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Characterization of Interferon-α 13, a Novel Constitutive Murine Interferon-α Subtype

Pesch

Michiels

2003

Journal of Biological Chemistry

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Viruses were titrated on BHK-21 cells by a standard plaque assay. BHK-21, COS-7, BALB/3T3, and L929 cells were cultured as described previously (29).…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Characterization of Interferon-α 13, a Novel Constitutive Murine Interferon-α Subtype

Pesch

Michiels

2003

Journal of Biological Chemistry

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“…The L protein is produced by all members of the Cardiovirus genus and has been implicated in in vivo persistence because it modulates the host antiviral response (8,34,39). Although analysis revealed that the L protein is the second most divergent region across TMEV strains (Fig.…”

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confidence: 99%

Identification of a Novel Neuropathogenic Theiler's Murine Encephalomyelitis Virus

Buckwalter

Nga

Gouilh

et al. 2011

J Virol

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Theiler's murine encephalitis viruses (TMEV) are divided into two subgroups based on their neurovirulence. Persistent strains resemble Theiler's original viruses (referred to as the TO subgroup), which largely induce a subclinical polioencephalomyelitis during the acute phase of the disease and can persist in the spinal cord of susceptible animals, inducing a chronic demyelinating disease. In contrast, members of the neurovirulent subgroup cause an acute encephalitis characterized by the rapid onset of paralysis and death within days following intracranial inoculation. We report herein the characterization of a novel neurovirulent strain of TMEV, identified using pyrosequencing technology and referred to as NIHE. Complete coverage of the NIHE viral genome was obtained, and it shares <90% nucleotide sequence identity to known TMEV strains irrespective of subgroup, with the greatest sequence variability being observed in genes encoding the leader and capsid proteins. The histopathological analysis of infected brain and spinal cord demonstrate inflammatory lesions and neuronal necrosis during acute infection with no evidence of viral persistence or chronic disease. Intriguingly, genetic analysis indicates the putative expression of the L* protein, considered a hallmark of strains within the persistent subgroup. Thus, the identification and characterization of a novel neurovirulent TMEV strain sharing features previously associated with both subgroups will lead to a deeper understanding of the evolution of TMEV strains and new insights into the determinants of neurovirulence.Theilioviruses have positive-sense, single-stranded RNA genomes and are members of the Picornaviridae family and the Cardiovirus genus. Several serotypes have been identified, causing disease in rodents, such as Theiler's murine encephalomyelitis virus (TMEV) (36, 37) and rat Theiler-like virus (RTV) (28), and humans, such as Vilyuisk human encephalomyelititis virus (VHEV) (6) and Saffold viruses (7,13,44). TMEV is an enteric pathogen that follows the fecal-oral route of infection; however, when inoculated intracranialy (IC), it can cause severe pathology in susceptible mouse strains. As a natural mouse pathogen, TMEV provides a valuable experimental model for understanding host-pathogen interactions. The TMEV serotype is divided into two subgroups based on the pathogenesis of the disease. Members of the TO subgroup, so named because they resemble Theiler's original strains (36), cause a biphasic infection. The early phase is an acute poliomyelitis characterized by viral replication in the neurons of the brain (1, 18). During the late phase of infection, the virus progresses from the gray to the white matter of the spinal cord, where, depending on the genetics of the mouse strain (4), it can persist for the life of the animal within various cell types (2, 21), causing in some instances chronic demyelination (19). In contrast, the second subgroup, consisting of the GDVII and FA strains, are neurovirulent, and their pathology is characterized by a...

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Replication of Theiler's virus requires NF‐κB‐activation: Higher viral replication and spreading in astrocytes from susceptible mice

Kang¹,

So²,

Park³

et al. 2008

Glia

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To investigate viral replication and cell-cell spreading in astrocytes, recombinant Theiler's murine encephalomyelitis virus (TMEV) expressing green fluorescent protein (GFP) during the replication was generated. GFP and TMEV proteins were processed correctly in infected cells and production of viral proteins could be tracked by fluorescent microscopy. Viral replication of both wild-type TMEV and GFP-TMEV was dependent on the activation of NF-kappaB and partially MAP kinase, based on chemical inhibition studies. Viral replication was significantly reduced in primary astrocytes from NF-kappaB1 (p105)-deficient mice compared with that from wild-type control mice, whereas cytokine production was enhanced. These results suggest an association of canonical NF-kappaB subunits in viral replication, but not cytokine production. Viral replication was also suppressed in both IKKalpha and IKKbeta-deficient mouse embryonic fibroblasts (MEFs), compared with that in wild-type MEF. However, the inhibition was significantly greater in IKKbeta-deficient MEF, suggesting that IKKbeta plays a stronger role in supporting viral replication. Interestingly, viral replication and spreading in primary astrocytes from susceptible SJL/J mice were several-fold higher than those in astrocytes from resistant C57BL/6 mice, suggesting that higher viral replication levels in astrocytes may also contribute to the viral persistence in the central nervous system (CNS) of susceptible SJL/J mice. A relatively higher level of activated NF-kappaB was found in the nuclei of virus-infected SJL astrocytes compared with C57BL/6 astrocytes suggest that the NF-kappaB activation level affects on viral replication.

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The Leader Protein of Theiler's Virus Inhibits Immediate-Early Alpha/Beta Interferon Production

Cited by 115 publications

References 38 publications

Characterization of Interferon-α 13, a Novel Constitutive Murine Interferon-α Subtype

Characterization of Interferon-α 13, a Novel Constitutive Murine Interferon-α Subtype

Identification of a Novel Neuropathogenic Theiler's Murine Encephalomyelitis Virus

Replication of Theiler's virus requires NF‐κB‐activation: Higher viral replication and spreading in astrocytes from susceptible mice

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