Borna disease virus-specific circulating immune complexes, antigenemia, and free antibodies - the key marker triplet determining infection and prevailing in severe mood disorders

Borna disease virus (BDV), a unique genetically highly conserved RNA virus (Bornaviridae; Mononegavirales),(1) preferentially targets neurons of limbi c structures(2) causing behavioral abnormalities in animals.(3,4) Markers(5 -10) and virusl(11-13) in patients with affective disorders and schizophren ia have raised worldwide interest.(3) A persistent infection was suggestive from follow-up studies,(5,14) but inconstant detectability weakened a poss ible linkage.(15) This study for the first time discloses that detection ga ps are caused by BDV-specific circulating immune complexes (CIC), and their interplay with free antibodies and plasma antigens (p40/p24). Screening 30 00 sera each from human and equine patients over the past 4 years by new en zyme immunoassays (EIAs) revealed that BDV-CICs indicate 10 times higher in fection rates (up to 30% in controls, up to 100% in patients) than did prev ious serology,(16,17) Persistence of high amounts of CICs and plasma antige ns correlates with severity of depression. Even BDV RNA could be detected i n plasma samples with strong antigenemia. Our discovery not only explains t he course of persistent infection, but offers novel easy-to-use diagnostic tools by which new insights into BDV-related etiopathogenesis of disease an d epidemiology are possible.