Bornavirus infection in human diseases and its molecular neuropathology

Bornavirus is a non-cytolytic, neurotropic RNA virus that persistently infects the central nervous systems of vertebrates. Although bornavirus epidemiology has been investigated mainly in human psychiatric diseases for several decades, the involvement of persistent bornavirus infection in these diseases remains controversial. Recent studies have shown that two bornaviruses, Borna disease virus 1 and variegated squirrel bornavirus 1, can cause fatal encephalomyelitis in humans. In animal models, acute bornavirus infection causes immune-mediated encephalomyelitis, whereas persistent infection induces neurobehavioral disturbances resembling human neurodevelopmental disorders, such as autism. The neuropathology of persistent infection involves impairment in neural circuit formation and/or plasticity. Bornavirus P is a major pathogenic factor, which regulates neurite outgrowth, cell migration and synaptic plasticity. In addition, P disrupts the insulin-like growth factor pathway and induces Purkinje cell loss in the cerebellum, thereby causing autism-like neuropathology. Furthermore, bornavirus infection has been shown to disrupt neurogenesis. During neurogenesis, long interspersed nucleotide element-1, a retrotransposon, generates neuronal genomic and transcriptomic variances that are important for neural plasticity. Long interspersed nucleotide element-1 retrotranspose their own mRNAs in uninfected cells, whereas they also retrotranspose bornavirus mRNAs in infected cells; therefore, the long interspersed nucleotide element-1 retrotransposition required for neural plasticity might be disturbed by infections. The aim of the present article is to provide fundamental information on bornavirus infection in humans. Clinicians should consider bornavirus infection in at least two types of suspicious cases: non-purulent fatal encephalitis with unknown etiology among patients who have had contact with animals or lived in a rural area and those related to organ transplantation.