THE NEUROPATHOGENESIS OF BORNA-DISEASE VIRUS-INFECTIONS

The unique genetic and biological properties of this small enveloped R NA virus indicate that Borna disease virus (BDV) is an evolutionary ol d pathogen. It appears perfectly adapted to persist inside the limbic system, a most delicate and sensitive old area of the mammalian brain involved in the control of mood, behavior, and memory. In many infecte d individuals, BDV remains a commensal during their lifetime. In a min ority of vulnerable subjects, BDV becomes frequently activated, leadin g to episodes of distinct, more or less severe disturbances of informa tion processing, behavioral and mood alterations. BDV research in huma ns is anticipated to initiate new insights into the interplay of exoge nous and endogenous factors governing mood disorders. In nature BDV pr eferentially behaves as a neurotropic virus, but may latently and/or p ersistently infect cells of the reticuloendothelial system. This has b een shown to be of great diagnostic importance, because now BDV 'footp rints' can be followed in vivo in animals and man. BDV, which has long been considered as a classical animal virus, is present in humans, an d has been found to be associated with some defined psychiatric disord ers in particularly vulnerable individuals. An interaction of BDV prot eins with neurotransmitter activities is plausible in the light of exp erimental animal data. Interference with normal behavior and the influ ence on mood and cognitive functions as demonstrated in animals and as sumed in humans require extensive future research on the molecular eti opathogenesis. Aside from these clinical aspects, BDV is an unusual ag ent with outstanding features, namely replication in the nucleus of it s target cells by an elusive, partially unknown mechanism, showing no cytopathogenicity or disturbance of vital cell functions, but altering luxury functions, and with a lifelong persistence giving rise to peri ods of long latency and short activation.