Viral replicase is used to create multiple strands of negative RNA which bind to nucleoprotein to produce multiple nucleocapsids. Two theories of entry into neurons include non-specific endocytosis and inclusion of viral particles during synaptic neurotransmitter vesicle recycling. The main response is increased IgG, but IgM may also increase. Cytotoxic T cell response usually appears 4 to 6 days after infection and the humoral response peaks 8 days and then rapidly declines after infection with some viral strains. Interferon levels also rise and remain elevated until death.
Viral particles accumulate in neurons and disrupt their physiological process.
Incubation period ranges from 21 days to 80 days or possibly several years and is largely dependent on site of infection. If neurons far from the head region are infected, then it may take longer for the virus to migrate to and infect the brain than if neurons close to the head are infected. Mouse inoculation tests or tissue culture techniques utilizing neuroblastoma cells are also used. Alternatively, direct immunofluorescent antibody testing of skin or hair follicles can be performed on suspect animals. However, the number of cases reported is decreasing annually.