Pathogenesis of haemagglutinating encephalomyelitis virus (HEV) in mice experimentally infected by different routes

Three-day-old suckling mice inoculated intracerebrally (i.c.) with the 67N strain of haemagglutinating encephalomyelitis virus (HEV) showed nervous signs and died. The virus was passaged 10 times in suckling mice and was designated the MB-67N strain. The pathogenesis of MB-67N was studied with various ages of mice and inoculation routes. All mice inoculated i.c. with a large dose of virus died regardless of age, although a smaller dose caused fatal infection only in suckling mice. By intranasal, intraperitoneal and subcutaneous inoculation, the virus also killed suckling mice under 16 days old, but not older mice, even with a large dose. The susceptibility of mice for the MB-67N strain was influenced by age and inoculation routes. High titres of virus were re-isolated from the brain of diseased mice after inoculation by any route, but not from other organs. Histologically, numerous areas of severe focal necrosis were produced in the cerebral cortex. Specific immuno-fluorescence and numerous viral particles were found in the cytoplasm of nerve cells by immuno-fluorescence staining and electron microscopy. These findings indicate that the MB-67N propagates mainly in the central nervous system and nerve cells serve as a main target of virus replication.