title: Identification of a novel neuropathogenic Theiler's murine encephalomyelitis virus.
abstract: 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.
authors.affiliation: Laboratory of Dendritic Cell Immunobiology, Department of Immunology, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris, Cedex 15, France.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Buckwalter
authors.forename: Phan Thi
authors.initials: PT
authors.lastname: Nga
authors.forename: Meriadeg Ar
authors.initials: MA
authors.lastname: Gouilh
authors.forename: Laurence
authors.initials: L
authors.lastname: Fiette
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Bureau
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Laird
authors.forename: Julian
authors.initials: J
authors.lastname: Buchrieser
authors.forename: Simona
authors.initials: S
authors.lastname: Ozden
authors.forename: Justine
authors.initials: J
authors.lastname: Cheval
authors.forename: Marc
authors.initials: M
authors.lastname: Eloit
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Manuguerra
authors.forename: Antoine
authors.initials: A
authors.lastname: Gessain
authors.forename: Paul T
authors.initials: PT
authors.lastname: Brey
authors.forename: Arnaud
authors.initials: A
authors.lastname: Fontanet
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Albert
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology; D002213:Capsid / Q000737:chemistry; D016679:Genome, Viral; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D013116:Spinal Cord / Q000473:pathology / Q000821:virology; D017945:Theilovirus / Q000145:classification / Q000302:isolation & purification* / Q000472:pathogenicity; D056189:Viral Tropism