Abstract
Borna disease virus (BDV) is a non-cytolytic, neurotropic RNA virus that can infect a wide variety of vertebrate species from birds and primates to humans. Several studies have been carried out to investigate whether BDV is associated with neuropsychiatric diseases. However, this association is still inconclusive. Two panels of subjects consisting of 1,679 various neuropsychiatric patients and healthy people from three western China provinces were enrolled in this study. BDV p24 or p40 RNA in peripheral blood mononuclear cells (PBMCs) were detected in the first panel of 1,481 subjects using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and cerebrospinal fluid (CSF) samples from the BDV RNA-positive individuals were subjected to BDV p24 antibodies testing by enzyme-linked immunosorbent assay (ELISA). BDV p24 or p40 RNA in PBMCs and p24 antibodies in plasma were detected in the second panel of 198 subjects by RT-qPCR and Western blot. A higher prevalence for BDV RNA was demonstrated in patients with viral encephalitis (6.70 %), Guillain–Barré syndrome (6.70 %), schizophrenia (9.90 %) and chronic fatigue syndrome (CFS) (12.70 %) compared to healthy controls in the first panel. CSF p24 antibodies were demonstrated in three viral encephalitis patients, two schizophrenia patients and two major depressive disorder (MDD) patients. The prevalences of p24 antibodies in plasma from patients with viral encephalitis (13.24 %), multiple sclerosis (25.00 %) and Parkinson’s disease (22.73 %) were significantly higher than healthy controls. This study demonstrates that BDV infection also exists in humans from three western China provinces, and suggests the involvement of the contribution of BDV in the aetiology of Chinese patients with some neuropsychiatric disorders, including viral encephalitis, schizophrenia, CFS, multiple sclerosis and Parkinson’s disease.
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References
Horie M, Honda T, Suzuki Y, Kobayashi Y, Daito T, Oshida T, Ikuta K, Jern P, Gojobori T, Coffin JM, Tomonaga K (2010) Endogenous non-retroviral RNA virus elements in mammalian genomes. Nature 463:84–87
Bode L, Ludwig H (2003) Borna disease virus infection, a human mental-health risk. Clin Microbiol Rev 16:534–545
Dürrwald R, Ludwig H (1997) Borna disease virus (BDV), a (zoonotic?) worldwide pathogen. A review of the history of the disease and the virus infection with comprehensive bibliography. Zentralbl Veterinarmed B 44:147–184
Briese T, Schneemann A, Lewis AJ, Park YS, Kim S, Ludwig H, Lipkin WI (1994) Genomic organization of Borna disease virus. Proc Natl Acad Sci U S A 91:4362–4366
Cubitt B, Oldstone C, de la Torre JC (1994) Sequence and genome organization of Borna disease virus. J Virol 68:1382–1396
de la Torre JC, Bode L, Carbone KM, Dietzschold B, Ituka K, Lipkin IW, Ludwig H, Richt JA, Staeheli P, Stitz L (2000) Family Bornaviridae. In: van Regenmortel MHV, Fauquet CM, Bishop DHL (eds) Virus taxonomy: classification and nomenclature of viruses: seventh report of the International Committee on Taxonomy of Viruses. Academic Press, London, pp 531–538
Pletnikov MV, Gonzalez-Dunia D, Stitz L (2002) Experimental infection: pathogenesis of neurobehavioral disease. In: Carbone KM (ed) Borna disease virus and its role in neurobehavioral disease, 1st edn. American Society for Microbiology (ASM) Press, Washington, pp 125–178
Matsumoto Y, Hayashi Y, Omori H, Honda T, Daito T, Horie M, Ikuta K, Fujino K, Nakamura S, Schneider U, Chase G, Yoshimori T, Schwemmle M, Tomonaga K (2012) Bornavirus closely associates and segregates with host chromosomes to ensure persistent intranuclear infection. Cell Host Microbe 11:492–503
Kinnunen PM, Palva A, Vaheri A, Vapalahti O (2013) Epidemiology and host spectrum of Borna disease virus infections. J Gen Virol 94:247–262
Ludwig H, Bode L (2000) Borna disease virus: new aspects on infection, disease, diagnosis and epidemiology. Rev Sci Tech 19:259–288
Rott R, Herzog S, Fleischer B, Winokur A, Amsterdam J, Dyson W, Koprowski H (1985) Detection of serum antibodies to Borna disease virus in patients with psychiatric disorders. Science 228:755–756
Bode L, Zimmermann W, Ferszt R, Steinbach F, Ludwig H (1995) Borna disease virus genome transcribed and expressed in psychiatric patients. Nat Med 1:232–236
Lipkin WI, Briese T, Hornig M (2011) Borna disease virus—fact and fantasy. Virus Res 162:162–172
Chalmers RM, Thomas DR, Salmon RL (2005) Borna disease virus and the evidence for human pathogenicity: a systematic review. QJM 98:255–274
Arias I, Sorlozano A, Villegas E, de Dios Luna J, McKenney K, Cervilla J, Gutierrez B, Gutierrez J (2012) Infectious agents associated with schizophrenia: a meta-analysis. Schizophr Res 136:128–136
Li Q, Wang Z, Zhu D, Xu M, Chen X, Peng D, Iwata Y, Xie P (2009) Detection and analysis of Borna disease virus in Chinese patients with neurological disorders. Eur J Neurol 16:399–403
Chen CH, Chiu YL, Shaw CK, Tsai MT, Hwang AL, Hsiao KJ (1999) Detection of Borna disease virus RNA from peripheral blood cells in schizophrenic patients and mental health workers. Mol Psychiatry 4:566–571
Thakur R, Sarma S, Sharma B (2009) Role of Borna disease virus in neuropsychiatric illnesses: are we inching closer? Indian J Med Microbiol 27:191–201
Schindler AR, Vögtlin A, Hilbe M, Puorger M, Zlinszky K, Ackermann M, Ehrensperger F (2007) Reverse transcription real-time PCR assays for detection and quantification of Borna disease virus in diseased hosts. Mol Cell Probes 21:47–55
Wensman JJ, Thorén P, Hakhverdyan M, Belák S, Berg M (2007) Development of a real-time RT-PCR assay for improved detection of Borna disease virus. J Virol Methods 143:1–10
Johansson M, Berg M, Berg AL (2002) Humoral immune response against Borna disease virus (BDV) in experimentally and naturally infected cats. Vet Immunol Immunopathol 90:23–33
Lieb K, Staeheli P (2001) Borna disease virus—does it infect humans and cause psychiatric disorders? J Clin Virol 21:119–127
Evengård B, Briese T, Lindh G, Lee S, Lipkin WI (1999) Absence of evidence of Borna disease virus infection in Swedish patients with Chronic Fatigue Syndrome. J Neurovirol 5:495–499
Bode L, Komaroff AL, Ludwig H (1992) No serologic evidence of borna disease virus in patients with chronic fatigue syndrome. Clin Infect Dis 15:1049
Kitani T, Kuratsune H, Fuke I, Nakamura Y, Nakaya T, Asahi S, Tobiume M, Yamaguti K, Machii T, Inagi R, Yamanishi K, Ikuta K (1996) Possible correlation between Borna disease virus infection and Japanese patients with chronic fatigue syndrome. Microbiol Immunol 40:459–462
Nakaya T, Takahashi H, Nakamura Y, Asahi S, Tobiume M, Kuratsune H, Kitani T, Yamanishi K, Ikuta K (1996) Demonstration of Borna disease virus RNA in peripheral blood mononuclear cells derived from Japanese patients with chronic fatigue syndrome. FEBS Lett 378:145–149
Yamaguchi K, Sawada T, Naraki T, Igata-Yi R, Shiraki H, Horii Y, Ishii T, Ikeda K, Asou N, Okabe H, Mochizuki M, Takahashi K, Yamada S, Kubo K, Yashiki S, Waltrip RW 2nd, Carbone KM (1999) Detection of borna disease virus-reactive antibodies from patients with psychiatric disorders and from horses by electrochemiluminescence immunoassay. Clin Diagn Lab Immunol 6:696–700
Nakaya T, Takahashi H, Nakamur Y, Kuratsune H, Kitani T, Machii T, Yamanishi K, Ikuta K (1999) Borna disease virus infection in two family clusters of patients with chronic fatigue syndrome. Microbiol Immunol 43:679–689
Güngör S, Anlar B, Turan N, Yilmaz H, Helps CR, Harbour DA (2005) Antibodies to borna disease virus in subacute sclerosing panencephalitis. Pediatr Infect Dis J 24:833–834
Bechter K, Schüttler R, Herzog S (1992) Borna disease virus: possible causal agent in psychiatric and neurological disorders in two families. Psychiatry Res 42:291–294
Ludwig H, Thein P (1977) Demonstration of specific antibodies in the central nervous system of horses naturally infected with Borna disease virus. Med Microbiol Immunol 163:215–226
Kao M, Hamir AN, Rupprecht CE, Fu ZF, Shankar V, Koprowski H, Dietzschold B (1993) Detection of antibodies against Borna disease virus in sera and cerebrospinal fluid of horses in the USA. Vet Rec 132:241–244
Deuschle M, Bode L, Heuser I, Schmider J, Ludwig H (1998) Borna disease virus proteins in cerebrospinal fluid of patients with recurrent depression and multiple sclerosis. Lancet 352:1828–1829
Kitze B, Herzog S, Rieckmann P, Poser S, Richt J (1996) No evidence of Borna disease virus-specific antibodies in multiple sclerosis patients in Germany. J Neurol 243:660–662
Sierra-Honigmann AM, Carbone KM, Yolken RH (1995) Polymerase chain reaction (PCR) search for viral nucleic acid sequences in schizophrenia. Br J Psychiatry 166:55–60
Bode L, Reckwald P, Severus WE, Stoyloff R, Ferszt R, Dietrich DE, Ludwig H (2001) Borna disease virus-specific circulating immune complexes, antigenemia, and free antibodies—the key marker triplet determining infection and prevailing in severe mood disorders. Mol Psychiatry 6:481–491
Rackova S, Janu L, Kabickova H (2009) Borna disease virus circulating immunocomplex positivity and psychopathology in psychiatric patients in the Czech Republic. Neuro Endocrinol Lett 30:414–420
Patti AM, Vulcano A, Candelori E, Ludwig H, Bode L (2008) Borna disease virus infection in the population of Latium (Italy). APMIS Suppl (124):74–76
Fu ZF, Amsterdam JD, Kao M, Shankar V, Koprowski H, Dietzschold B (1993) Detection of Borna disease virus-reactive antibodies from patients with affective disorders by western immunoblot technique. J Affect Disord 27:61–68
Kishi M, Nakaya T, Nakamura Y, Kakinuma M, Takahashi TA, Sekiguchi S, Uchikawa M, Tadokoro K, Ikeda K, Ikuta K (1995) Prevalence of Borna disease virus RNA in peripheral blood mononuclear cells from blood donors. Med Microbiol Immunol 184:135–138
Sauder C, Müller A, Cubitt B, Mayer J, Steinmetz J, Trabert W, Ziegler B, Wanke K, Mueller-Lantzsch N, de la Torre JC, Grässer FA (1996) Detection of Borna disease virus (BDV) antibodies and BDV RNA in psychiatric patients: evidence for high sequence conservation of human blood-derived BDV RNA. J Virol 70:7713–7724
Chen CH, Chiu YL, Wei FC, Koong FJ, Liu HC, Shaw CK, Hwu HG, Hsiao KJ (1999) High seroprevalence of Borna virus infection in schizophrenic patients, family members and mental health workers in Taiwan. Mol Psychiatry 4:33–38
Terayama H, Nishino Y, Kishi M, Ikuta K, Itoh M, Iwahashi K (2003) Detection of anti-Borna Disease Virus (BDV) antibodies from patients with schizophrenia and mood disorders in Japan. Psychiatry Res 120:201–206
Haga S, Motoi Y, Ikeda K (1997) Borna disease virus and neuropsychiatric disorders. The Japan Bornavirus Study Group. Lancet 350:592–593
Bechter K, Herzog S, Behr W, Schüttler R (1995) Investigations of cerebrospinal fluid in Borna disease virus seropositive psychiatric patients. Eur Psychiatry 10:250–258
Acknowledgements
This work was financially supported by the National Basic Research Program of China (973 Program) (Grant No. 2009CB918302) and the National Natural Science Foundation of China (Grant No. 31160210).
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The authors declare no financial or other conflict of interests.
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L. Zhang, M.-M. Xu, L. Zeng and S. Liu contributed equally to this work.
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Zhang, L., Xu, MM., Zeng, L. et al. Evidence for Borna disease virus infection in neuropsychiatric patients in three western China provinces. Eur J Clin Microbiol Infect Dis 33, 621–627 (2014). https://doi.org/10.1007/s10096-013-1996-4
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DOI: https://doi.org/10.1007/s10096-013-1996-4