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

2001 ◽  
Vol 75 (17) ◽  
pp. 7811-7817 ◽  
Author(s):  
Vincent van Pesch ◽  
Olivier van Eyll ◽  
Thomas Michiels
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Zinc Binding ◽  
Binding Motif ◽  
Theiler's Virus ◽  
L Protein ◽  
Beta Interferon ◽  
The Central Nervous System ◽  
Alpha Beta ◽  
Zinc Binding Motif

ABSTRACT Theiler's virus is a picornavirus responsible for a persistent infection of the central nervous system of the mouse, leading to a chronic demyelinating disease considered to be a model for multiple sclerosis. The leader (L) protein encoded by Theiler's virus is a 76-amino-acid-long peptide containing a zinc-binding motif. This motif is conserved in the L proteins of all cardioviruses, including encephalomyocarditis virus. The L protein of Theiler's virus was suggested to interfere with the alpha/beta interferon (IFN-α/β) response (W.-P. Kong, G. D. Ghadge, and R. P. Roos, Proc. Natl. Acad. Sci. USA 91:1796–1800, 1994). We show that expression of the L protein indeed inhibits the production of alpha/beta interferon by infected L929 cells. The L protein specifically inhibits the transcription of the IFN-α4 and IFN-β genes, which are known to be activated early in response to viral infection. Mutation of the zinc finger was sufficient to block the anti-interferon activity, outlining the importance of this motif in the L protein function. In agreement with the anti-interferon role of the L protein, a virus bearing a mutation in the zinc-binding motif was dramatically impaired in its ability to persist in the central nervous system of SJL/J mice.

The shiverer mutation affects the persistence of Theiler's virus in the central nervous system.

1997 ◽  
Vol 71 (7) ◽  
pp. 5025-5030 ◽  
Author(s):  
F Bihl ◽  
C Pena-Rossi ◽  
J L Guénet ◽  
M Brahic ◽  
J F Bureau
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Theiler's Virus ◽  
The Central Nervous System

scholarly journals The Majority of Infiltrating CD8+ T Cells in the Central Nervous System of Susceptible SJL/J Mice Infected with Theiler's Virus Are Virus Specific and Fully Functional

2002 ◽  
Vol 76 (13) ◽  
pp. 6577-6585 ◽  
Author(s):  
Bong-Su Kang ◽  
Michael A. Lyman ◽  
Byung S. Kim
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
T Cell ◽  
Demyelinating Disease ◽  
Class I ◽  
Theiler's Virus ◽  
Ctl Response ◽  
The Central Nervous System ◽  
Ifn Γ

ABSTRACT Theiler's virus infection of the central nervous system (CNS) induces an immune-mediated demyelinating disease in susceptible mouse strains, such as SJL/J, and serves as a relevant infectious model for human multiple sclerosis. It has been previously suggested that susceptible SJL/J mice do not mount an efficient cytotoxic T-lymphocyte (CTL) response to the virus. In addition, genetic studies have shown that resistance to Theiler's virus-induced demyelinating disease is linked to the H-2D major histocompatibility complex class I locus, suggesting that a compromised CTL response may contribute to the susceptibility of SJL/J mice. Here we show that SJL/J mice do, in fact, generate a CD8+ T-cell response in the CNS that is directed against one dominant (VP3159-166) and two subdominant (VP111-20 and VP3173-181) capsid protein epitopes. These virus-specific CD8+ T cells produce gamma interferon (IFN-γ) and lyse target cells in the presence of the epitope peptides, indicating that these CNS-infiltrating CD8+ T cells are fully functional effector cells. Intracellular IFN-γ staining analysis indicates that greater than 50% of CNS-infiltrating CD8+ T cells are specific for these viral epitopes at 7 days postinfection. Therefore, the susceptibility of SJL/J mice is not due to the lack of an early functional Theiler's murine encephalomyelitis virus-specific CTL response. Interestingly, T-cell responses to all three epitopes are restricted by the H-2Ks molecule, and this skewed class I restriction may be associated with susceptibility to demyelinating disease.

scholarly journals H-2Db−/− Mice Are Susceptible to Persistent Infection by Theiler's Virus

2000 ◽  
Vol 74 (12) ◽  
pp. 5470-5476 ◽  
Author(s):  
Arièle Azoulay-Cayla ◽  
Sven Dethlefs ◽  
Béatrice Pérarnau ◽  
Eva-Lotta Larsson-Sciard ◽  
François A. Lemonnier ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
T Lymphocyte ◽  
Persistent Infection ◽  
Cytotoxic T Lymphocyte ◽  
Target Cells ◽  
Theiler's Virus ◽  
Ctl Response ◽  
The Central Nervous System

ABSTRACT H-2b mice are resistant to persistent infection of the central nervous system by Theiler's virus. They clear the infection 7 to 10 days after intracranial inoculation. Resistance maps to the H-2D gene and not to the H-2K gene and is associated with a potent antiviral cytotoxic T-lymphocyte (CTL) response. We used H-2b mice in which theH-2D or the H-2K gene had been inactivated to dissect the respective roles of these genes in resistance. We report that H-2D −/− but notH-2K −/− mice were susceptible to persistent infection. Furthermore, whereas H-2K −/−mice mounted a vigorous virus-specific CTL response, similar to that of control C57BL/6 mice, the CTL response ofH-2D −/− mice was nil or minimal. Using target cells transfected with the H-2Db or theH-2Kb gene, we showed that theH-2K-restricted CTL response against the virus was minimal in H-2D −/− mice. These results demonstrate that the H-2Db andH-2Kb genes play nonredundant roles in the resistance to this persistent infection.

scholarly journals Epitope-Tagged L* Protein of Theiler's Murine Encephalomyelitis Virus Is Expressed in the Central Nervous System in the Acute Phase of Infection

2002 ◽  
Vol 76 (24) ◽  
pp. 13049-13054 ◽  
Author(s):  
Kunihiko Asakura ◽  
Harunobu Murayama ◽  
Toshiki Himeda ◽  
Yoshiro Ohara
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Phase ◽  
Wild Type Virus ◽  
Theiler's Murine Encephalomyelitis Virus ◽  
L Protein ◽  
Theiler’S Murine Encephalomyelitis Virus ◽  
Encephalomyelitis Virus ◽  
The Central Nervous System ◽  
Resistant Strains

ABSTRACT TO subgroup strains of Theiler's murine encephalomyelitis virus (TMEV) synthesize L* protein from an alternative initiation codon. We first demonstrated L* expression in the central nervous system (CNS) of TMEV-infected mice during the acute phase of infection by immunoprecipitation and immunoblotting with anti-L* antibody. In addition, we generated mutant viruses which synthesize FLAG or 3xFLAG epitope-tagged L* protein. With a mutant virus expressing 3xFLAG epitope-tagged L*, designated DA/3xFLAGL*, we investigated L* in the CNS in the acute phase of infection. DA/3xFLAGL* did not change the virus tropism in comparison with wild-type virus, and L* was clearly identified in the CNS in both susceptible and resistant strains of mice. Double immunolabeling studies showed that L* is colocalized with TMEV polyprotein and exclusively expressed in neurons.

scholarly journals Viral Load Increases in SJL/J Mice Persistently Infected by Theiler's Virus after Inactivation of the β2m Gene

2001 ◽  
Vol 75 (16) ◽  
pp. 7723-7726 ◽  
Author(s):  
Stéphanie Aubagnac ◽  
Michel Brahic ◽  
Jean-François Bureau
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Viral Load ◽  
Viral Rna ◽  
Class I ◽  
Theiler's Virus ◽  
Persistently Infected ◽  
The Central Nervous System ◽  
I Gene

ABSTRACT We show that inactivating the β 2 m gene increases the viral load of SJL/J mice persistently infected by Theiler's virus. Together with previous results, this shows that the characteristics ofTmevp1, a locus which controls the amount of viral RNA that persists in the central nervous system, are those of an H-2class I gene.

scholarly journals A TRANSMISSIBLE AGENT (THEILER'S VIRUS) IN THE INTESTINES OF NORMAL MICE

1940 ◽  
Vol 72 (2) ◽  
pp. 113-127 ◽  
Author(s):  
Peter K. Olitsky
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Carrier State ◽  
Theiler's Virus ◽  
Rockefeller Institute ◽  
Intracerebral Inoculation ◽  
Low Degree ◽  
Intestinal Contents ◽  
The Central Nervous System ◽  
Normal Stock

Every experiment with the contents of one, or with those pooled from two to five of the normal stock of Rockefeller Institute strain of albino mice, 1 to 2 months of age, revealed the presence of a virus which, after intracerebral inoculation into normal mice, induced characteristic paralytic encephalomyelitis, indistinguishable from Theilerapos;s disease. No difference was seen in this effect of intestinal contents deriving from animals paralyzed during the course of spontaneous encephalomyelitis and from normal mice. The influence of age on carriage of virus, as well as on the persistence of the carrier state, is discussed. The present, as well as previous work has shown that the virus found in normal (or paralyzed) mice is similar to that of Theiler's disease in all of its properties thus far investigated; among the strains of the latter now at hand it can be classified with those having a low degree of invasiveness after peripheral inoculation. The virus has thus far been recovered from intestinal contents, intestinal walls, and mesenteric glands but not from the central nervous system of normal mice; from these sites, as well as from the central nervous system, in paralyzed mice. In order of concentration of virus, the contents have more, the walls less, and the glands least.

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