Hydrocephalus in mice infected with a Theiler's murine encephalomyelitis virus variant.
The etiology of hydrocephalus is never established in the majority of clinical cases, while various agents, nutritional deficiencies, and genetic factors have been shown to play a role. Viral infection has been recognized as one of the causative factors in the development of hydrocephalus. The wild-type DA strain of Theiler's murine encephalomyelitis virus (TMEV), which belongs to the family Picornaviridae, causes a chronic demyelinating disease in mice with viral persistence that resembles multiple sclerosis. We found that a DA virus variant, hydrocephalus 101 virus (H101 virus), caused hydrocephalus in mice, a condition previously never described for TMEV. To clarify the relationship between DA virus infection and hydrocephalus, we compared H101 virus and wild-type DA virus infection in mice. Using immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL), we found that during the acute phase of infection, H101 virus caused macrocephaly and meningitis with the presence of apoptosis, while parenchymal involvement was not evident. In contrast, wild-type DA virus caused an acute polioencephalomyelitis with parenchymal infection and apoptosis. During the chronic phase, H101 virus infection caused communicating hydrocephalus without viral persistence. No demyelination and little or no anti-TMEV antibodies were observed in H101 virus-infected mice. Sequence analysis revealed that H101 virus had mutations in the 5'UTR and capsid protein coding region. Characterization of this new hydrocephalus model gives insight into the possible viral involvement in human hydrocephalus cases of obscure etiology.
Tsunoda
I
I
Department of Neurology, University of Utah School of Medicine, Salt Lake City 84132, USA.
McCright
I J
IJ
Kuang
L Q
LQ
Zurbriggen
A
A
Fujinami
R S
RS
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D001483:Base Sequence; D002490:Central Nervous System / Q000821:virology; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D016679:Genome, Viral; D006849:Hydrocephalus / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D011051:Poliomyelitis / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D017945:Theilovirus / Q000235:genetics* / Q000276:immunology
D000914:Antibodies, Viral