Attenuation of neurovirulence of Theiler's murine encephalomyelitis virus strain GDVII is not sufficient to establish persistence in the central nervous system.

Lipton, Howard L.; Pritchard, A. E.; Calenoff, Miriam A.

doi:10.1099/0022-1317-79-5-1001

Cited by 10 publications

(6 citation statements)

References 14 publications

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“…In the present work, we show that an attenuated GDVII virus doesn't persist in the CNS of SJL/J mice. Our findings are in complete agreement with those recently reported by Lipton et al (14). Those authors attenuated the GDVII virus either by exchanging part of the 5Ј noncoding region with that of the BeAn virus or by deleting part of the L gene.…”

supporting

confidence: 94%

An Attenuated Variant of the GDVII Strain of Theiler’s Virus Does Not Persist and Does Not Infect the White Matter of the Central Nervous System

Jarousse¹,

Viktorova

Pilipenko

et al. 1999

J Virol

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The DA strain of Theiler’s virus causes a persistent and demyelinating infection of the white matter of spinal cord, whereas the GDVII strain causes a fatal gray-matter encephalomyelitis. Studies with recombinant viruses showed that this difference in phenotype is controlled mainly by the capsid. However, conflicting results regarding the existence of determinants of persistence in the capsid of the GDVII strain have been published. Here we show that a GDVII virus whose neurovirulence has been attenuated by an insertion in the 5′ noncoding region does not persist in the central nervous systems of mice. Furthermore, this virus infects the gray matter efficiently, but not the white matter. These results confirm the absence of determinants of persistence in the GDVII capsid. They suggest that the DA capsid controls persistence by allowing the virus to infect cells in the white matter of the spinal cord.

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supporting

confidence: 94%

An Attenuated Variant of the GDVII Strain of Theiler’s Virus Does Not Persist and Does Not Infect the White Matter of the Central Nervous System

Jarousse¹,

Viktorova

Pilipenko

et al. 1999

J Virol

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“…VOL. 17,2004 TMEV-INDUCED DEMYELINATING DISEASE AND MS 177 are in close contact on the virion surface (3,252,477). These residues, located around the edge of the "pit," may be in close proximity to a putative receptor-binding site (47).…”

Section: Determinants Of Viral Persistencementioning

confidence: 99%

“…In general, a chimeric GDVII virus, whose capsid had been replaced by that of the DA or the BeAn strain, was attenuated whereas a recombinant DA or BeAn virus with a GDVII capsid was virulent. However, mere attenuation of the neurovirulence of GDVII is not sufficient to established persistence (179,252). The significance of conformational differences via interaction of VP2 puff B and VP1 loop II between GDVII and DA viruses has been recently illustrated by generation of specific mutants (477).…”

Section: Determinants Of Viral Persistencementioning

confidence: 99%

Theiler's Virus Infection: a Model for Multiple Sclerosis

Chang²,

et al. 2004

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Both genetic background and environmental factors, very probably viruses, appear to play a role in the etiology of multiple sclerosis (MS). Lessons from viral experimental models suggest that many different viruses may trigger inflammatory demyelinating diseases resembling MS. Theiler's virus, a picornavirus, induces in susceptible strains of mice early acute disease resembling encephalomyelitis followed by late chronic demyelinating disease, which is one of the best, if not the best, animal model for MS. During early acute disease the virus replicates in gray matter of the central nervous system but is eliminated to very low titers 2 weeks postinfection. Late chronic demyelinating disease becomes clinically apparent approximately 2 weeks later and is characterized by extensive demyelinating lesions and mononuclear cell infiltrates, progressive spinal cord atrophy, and axonal loss. Myelin damage is immunologically mediated, but it is not clear whether it is due to molecular mimicry or epitope spreading. Cytokines, nitric oxide/reactive nitrogen species, and costimulatory molecules are involved in the pathogenesis of both diseases. Close similarities between Theiler's virus-induced demyelinating disease in mice and MS in humans, include the following: major histocompatibility complex-dependent susceptibility; substantial similarities in neuropathology, including axonal damage and remyelination; and paucity of T-cell apoptosis in demyelinating disease. Both diseases are immunologically mediated. These common features emphasize the close similarities of Theiler's virus-induced demyelinating disease in mice and MS in humans

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“…It does not persist in the CNSs of the rare survivors (16). Attenuated variants of this strain have been used recently to confirm its incapacity to persist (12,18). Importantly, the GDVII strain, which infects the gray matter, where it replicates almost exclusively in neurons (2,30), does not infect the white matter (12).…”

mentioning

confidence: 99%

The GDVII Strain of Theiler’s Virus Spreads via Axonal Transport

Martinat¹,

Jarousse²,

Prévost

et al. 1999

J Virol

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Following intracerebral inoculation, the DA strain of Theiler’s virus sequentially infects neurons in the gray matter and glial cells in the white matter of the spinal cord. It persists in the latter throughout the life of the animal. Several observations suggest that the virus spreads from the gray to the white matter by axonal transport. In contrast, the neurovirulent GDVII strain causes a fatal encephalitis with lytic infection of neurons. It does not infect the white matter of the spinal cord efficiently and does not persist in survivors. The inability of this virus to infect the white matter could be due to a defect in axonal transport. Using footpad inoculations, we showed that the GDVII strain is, in fact, transported in axons. Transport was prevented by sectioning the sciatic nerve. The kinetics of transport and experiments using colchicine suggested that the virus uses microtubule-associated fast axonal transport. Our results show that a cardiovirus can spread by fast axonal transport and suggest that the inability of the GDVII strain to infect the white matter is not due to a defect in axonal transport.

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Attenuation of neurovirulence of Theiler's murine encephalomyelitis virus strain GDVII is not sufficient to establish persistence in the central nervous system.

Cited by 10 publications

References 14 publications

An Attenuated Variant of the GDVII Strain of Theiler’s Virus Does Not Persist and Does Not Infect the White Matter of the Central Nervous System

An Attenuated Variant of the GDVII Strain of Theiler’s Virus Does Not Persist and Does Not Infect the White Matter of the Central Nervous System

Theiler's Virus Infection: a Model for Multiple Sclerosis

The GDVII Strain of Theiler’s Virus Spreads via Axonal Transport

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