HYDROCEPHALUS IN MICE INFECTED WITH A THEILERS MURINE ENCEPHALOMYELITIS VIRUS VARIANT

The etiology of hydrocephalus is never established in the majority of clinical cases, while various agents, nutritional deficiencies, and ge netic factors have been shown to play a role. Viral infection has been recognized as one of the causative factors in the development of hydr ocephalus. The wild-type DA strain of Theiler's murine encephalomyelit is virus (TMEV), which belongs to the family Picornaviridae, causes a chronic demyelinating disease in mice with viral persistence that rese mbles multiple sclerosis. We found that a DA virus variant. hydrocepha lus 101 virus (H101 virus), caused hydrocephalus in mice, a condition previously never described for TMEV. To clarify the relationship betwe en DA virus infection and hydrocephalus, we compared H101 virus and wi ld-type DA virus infection in mice. Using immunohistochemistry and ter minal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end label ing (TUNEL), we found that during the acute phase of infection, H101 v irus caused macrocephaly and meningitis with the presence of apoptosis , while parenchymal involvement was not evident. Ln contrast, wild-typ e DA virus caused an acute polioencephalomyelitis with parenchymal inf ection and apoptosis. During the chronic phase, H101 virus infection c aused communicating hydrocephalus without viral persistence, No demyel ination and Little or no anti-TMEV antibodies were observed in H101 vi rus-infected mice. Sequence analysis revealed that H101 virus had muta tions 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.