Murine forebrain anomalies induced by coxsackievirus B3 variants

Neonatal or 7-day-old mice inoculated intracranially with either of two temperature-sensitive mutants (ts1, ts6) or the parent coxsackievirus B3 (CVB3) subsequently developed porencephaly or hydranencephaly. The forebrain anomaly induced depended upon age of the animal at inoculation and virus variant inoculated. Sections of brains from hydranencephalic mice revealed severe meningeal reactions, necrotizing encephalitis, and liquifactive necrosis in the cerebrum. No pathology was found in the pons, medulla, or cerebellum. Immunofluorescence studies with hyperimmune anti-CVB3 antiserum showed a random distribution of virus-infected cells in the cerebrum. Virus was recovered from several organs but little to no interferon and no anti-CVB3 neutralizing antibody were present in brain tissues. Availability of cells for replication of virus at the time of inoculation and replicative properties of each virus likely contributed to the outcome. Thus, forebrain anomalies resembling those found in infants can be induced in a murine model by select variants of coxsackievirus B3.