Analysis of the Leader and Capsid Coding Regions of Persistent and Neurovirulent Strains of Theiler's Virus

Michiels, Thomas; Jarousse, Nadine; Brahic, Michel

doi:10.1006/viro.1995.0066

Cited by 55 publications

(55 citation statements)

References 11 publications

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“…The degree of identity shared by NIHE and known TMEV strains is Ͻ90% at the nucleotide level and Ͻ95% in its primary amino acid sequence (Tables 1 and 2). This is in contrast to the Ͼ99% identity for quasispecies variation seen for the TO4, WW, and DA strains (27) or the laboratory derivatives of S2 BeAn (14) or GDVII substrains (16,29).…”

contrasting

confidence: 70%

“…5B and C). Although it would be difficult to decipher an evolutionary history with such few numbers of sequenced strains, it has been hypothesized that neurovirulent strains have evolved from persistent strains (27). In summary, our study reports the discovery and characterization of a novel, highly neurovirulent TMEV, the first report of a new strain in this subgroup in more than 70 years.…”

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confidence: 78%

“…The majority of the sequence variation between NIHE and the other strains was clustered within the Ser/Thr-rich domain (62.5%) and the Theilo domain (79.5%). Interestingly, two positions in the Ser/Thr-rich region (L-55 and L-57) and one in the L-VP4 cleavage site (L-70) have been identified previously as distinguishing between the GDVII and TO strains (27,35). In all three instances, the NIHE sequence segregates with the TO strains.…”

mentioning

confidence: 82%

“…U32924 and M80883). Within these 3,262 bp, there is 99.7% identity to the GDVII strain, which has led to speculation that GDVII and FA actually are separate isolates of the same strain due to the time and place of isolation (27).…”

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confidence: 99%

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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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confidence: 70%

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confidence: 78%

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confidence: 82%

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confidence: 99%

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Identification of a Novel Neuropathogenic Theiler's Murine Encephalomyelitis Virus

Buckwalter

Nga

Gouilh

et al. 2011

J Virol

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“…The highest difference level was seen in the L peptide. In addition to the L peptide, some cardioviruses, in particular Theiler's murine encephalomyelitis virus strains that are associated with persistent infections, contain an alternate open reading frame (ORF), the so-called L* (14). As for the prototype SAF-V strain, the Can112051-06 putative L* ORF is unlikely to encode a protein because it has an ACG (instead of ATG) start codon (data not shown).…”

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confidence: 99%

New Saffold Cardioviruses in 3 Children, Canada

Abed

Boivin

2008

Emerg. Infect. Dis.

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Adaptation of Theiler's Virus to L929 Cells: Mutations in the Putative Receptor Binding Site on the Capsid Map to Neutralization Sites and Modulate Viral Persistence

Jnaoui

Michiels

1998

Virology

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Persistent strains of Theiler's virus, a murine picornavirus, produce a life-long infection of the central nervous system of the mouse and induce a chronic demyelinating disease. Strain DA1, a molecular clone of such a persistent strain, produces a prominent cytopathic effect in BHK-21 cells but is less efficient at infecting L929 cells. We cloned the cDNA of a derivative of virus DA1, adapted to promote a rapid cytopathic effect in L929 cells. Adaptation of the new variant (named KJ6) to L929 cells correlated with an enhanced viral entry rather than with an increased replication rate of the genome. Mutations responsible for L929 cells adaptation occurred in amino acids exposed at the surface of the capsid, in the CD loop of VP1 (100-102) and in the EF loop of VP2 (162-171-173), suggesting that these residues could be involved in receptor recognition. These two clusters of amino acids are precisely known to be part of neutralization epitopes. They also differentiate persistent from neurovirulent strains of Theiler's virus. Adaptation of the virus to L929 cells was accompanied by attenuation of its virulence for the mouse. Taken together, these data suggest a close relationship between receptor binding, virus neutralization, and virus phenotype.

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Analysis of the Leader and Capsid Coding Regions of Persistent and Neurovirulent Strains of Theiler's Virus

Cited by 55 publications

References 11 publications

Identification of a Novel Neuropathogenic Theiler's Murine Encephalomyelitis Virus

Identification of a Novel Neuropathogenic Theiler's Murine Encephalomyelitis Virus

New Saffold Cardioviruses in 3 Children, Canada

Adaptation of Theiler's Virus to L929 Cells: Mutations in the Putative Receptor Binding Site on the Capsid Map to Neutralization Sites and Modulate Viral Persistence

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