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Titre du document / Document title

Theiler's murine encephalomyelitis virus (TMEV) : Molecular aspects of its persistence

Auteur(s) / Author(s)

OHARA Y. (1) ; OBUCHI M. (1) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) Department of Microbiology, Kanazawa Medical University, Ishikawa, JAPON

Résumé / Abstract

Theiler's murine encephalomyelitis virus (TMEV) belongs to the genus Cardiovirus of the family Picornaviridae and is divided into two subgroups strains on the basis of their different biological activities. GDVII subgroup strains are highly virulent and produce acute fatal polioencephalomyelitis in mice. In the few surviving mice, neither viral persistence nor demyelination occurs. On the other hand, DA (or TO) subgroup strains are less virulent and cause a biphasic disease; although these strains produce milder polioencephalomyelitis in the acute stage of infection, mice recover and show primary demyelination one month or later after the infection. DA strain persists in the spinal cords of mice despite a vigorous humoral immune response. TMEV is thought to be an excellent animal model for the human demyelinating disease, multiple sclerosis. There are several interesting features regarding TMEV persistence. 1) A majority of TMEV-infected cells during the chronic stage of disease contain a relatively small number of copies of the genome (100-500 copies) which is insufficient for the induction of detectable expression of viral proteins. The limited viral protein synthesis is predicted to induce relatively little cytopathic effect, and therefore to allow the virus to bypass immunological clearance. 2) Sequence analysis of escape mutant viruses resistant to DA neutralizing monoclonal antibodies has identified four separate sites for amino acid mutations of capsid proteins that lead to a decrease in demyelinating activity. All of these sites are located on or near the rim of the 'pit', a putative receptor binding region of the virus. These findings suggest that antibody mediates neutralization by preventing the binding of virus to the cell receptor and that demyelination with virus persistence can be interfered with by preventing viral attachment to receptors of particular cell types. 3) Finally, a 17 kDa protein, designated as L*, is only synthesized in DA subgroup strains from an alternative, out-of-frame, initiation site. Studies of a DA mutant virus, which has an ACG rather than AUG at the L* initiation site and therefore does not synthesize L* protein, demonstrated that this protein is important for the virus growth in particular cell types and is critical for DA-induced demyelinating disease and virus persistence.

Revue / Journal Title

Recent research developments in virology  

Source / Source

Recent research developments in virology :   ( Vol. 1 (1999) - Part III )
1999  , pp. 897-918[Note(s) :  [456 p.]] (58 ref.) ISBN 81-86846-73-5 ;  Illustration : Illustration ;

Langue / Language

Anglais

Editeur / Publisher

INDE  (Revue)
Transworld research network, Trivandrum, INDE  (1999) (Monographie)

Mots-clés anglais / English Keywords

Review

;

Theiler murine encephalomyelitis virus

;

Mouse

;

Animal model

;

Pathogenesis

;

Persistence

;

Demyelination

;

Viral disease

;

Murine encephalomyelitis

;

Cardiovirus

;

Picornaviridae

;

Virus

;

Rodentia

;

Mammalia

;

Vertebrata

;

Infection

;

Central nervous system disease

;

Spinal cord disease

;

Cerebral disorder

;

Nervous system diseases

;

Mots-clés français / French Keywords

Article synthèse

;

Virus encéphalomyélite murine Theiler

;

Souris

;

Modèle animal

;

Pathogénie

;

Persistance

;

Démyélinisation

;

Virose

;

Encéphalomyélite murine

;

Cardiovirus

;

Picornaviridae

;

Virus

;

Rodentia

;

Mammalia

;

Vertebrata

;

Infection

;

Système nerveux central pathologie

;

Moelle épinière pathologie

;

Encéphale pathologie

;

Système nerveux pathologie

;

Mots-clés espagnols / Spanish Keywords

Artículo síntesis

;

Theiler murine encephalomyelitis virus

;

Ratón

;

Modelo animal

;

Patogenia

;

Persistencia

;

Desmielinización

;

Virosis

;

Encéfalomielitis murina

;

Cardiovirus

;

Picornaviridae

;

Virus

;

Rodentia

;

Mammalia

;

Vertebrata

;

Infección

;

Sistema nervosio central patología

;

Médula espinal patología

;

Encéfalo patología

;

Sistema nervioso patología

;

Localisation / Location

INIST-CNRS, Cote INIST : L 27470, 35400009052599.0240

Nº notice refdoc (ud4) : 1537965



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