Failure to Detect Borna Disease Virus Antibody and RNA from Peripheral Blood Mononuclear Cells of Psychiatric Patients

Article information

Psychiatry Investig. 2009;6(4):306-312
Publication date (electronic) : 2009 November 05
doi :
1Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea.
2Department of Microbiology, College of Medicine, Korea University, Seoul, Korea.
3Division of Brain Korea 21 Biomedical Science, Korea University, Seoul, Korea.
Correspondence: Yong-Ku Kim, MD, PhD. Department of Psychiatry, College of Medicine, Korea University, Ansan Hospital, 516 Gojan-dong, Danwon-gu, Ansan 425-020, Korea. Tel +82-31-412-5140, Fax +82-31-412-5144,
Received 2009 July 08; Revised 2009 September 11; Accepted 2009 September 29.



Borna disease virus (BDV) is a highly neurotropic agent causing various neuropsychiatric symptoms in animals. Over the past two decades, it has been suggested that BDV might be associated with human psychiatric diseases. We aimed to investigate whether BDV is associated with psychiatric patients in Korea.


We recruited 60 normal controls and 198 psychiatric patients (98 patients with depressive disorder, 60 with schizophrenia, and 40 with bipolar disorder). We used an indirect immunofluorescence antibody (IFA) test for the BDV antibody and a real-time reverse transcriptase polymerase chain reaction (rRT-PCR) assay for p24 and p40 RNA from peripheral blood mononuclear cells (PBMCs).


Neither the BDV antibody nor p24, p40 RNA was detected in controls and patients groups.


Our results suggest that BDV might not be associated with psychiatric patients in Korea.


It has been suggested that viruses may cause various psychiatric diseases such as schizophrenia and mood disorders.1 Borna disease virus (BDV) is one of the possible causative agents associated with psychiatric diseases. BDV is a highly neurotropic RNA virus with an enveloped, nonsegmented, negative stranded RNA genome.2-4 BDV has been known to naturally infect several animal species such as cattle, cats, horses, and sheep.5-8

Animals infected with BDV show various neurobehavioral symptoms, such as hyperactivity, stereotyped behavior, anxiety, and abnormal social behaviors reminiscent of symptoms observed in human psychiatric diseases.9-11 BDV mainly infects the limbic system and cerebellum, which play an important role in the psychiatric disease.12-14 Recent studies have further demonstrated evidence that BDV causes disturbances in the central nervous system.15-17

Based on those findings, several studies have been carried out to investigate whether BDV is associated with psychiatric diseases. Initially, Rott et al.18 detected antibodies against BDV mainly in mood disorder patients. With the knowledge of the sequence and genomic organization of BDV, Bode et al.19 first detected BDV RNA by reverse transcriptase polymerase chain reaction (RT-PCR) in various psychiatric patients. Other investigators have revealed the possible relationship between BDV and human psychiatric diseases in various regions such as Europe,20-22 Brazil,23,24 and Japan.13,25,26 However, due to the lack of reliable diagnostic tools for BDV detection, subsequent studies could not replicate BDV-positive results (Table 1), and it remains unclear whether BDV is associated with human psychiatric diseases.27


Published studies of BDV detection by RT-PCR in neuropsychiatric samples of human peripheral blood

Recently, real time RT-PCR (rRT-PCR) has been proven to be an effective and convenient method in viral gene detection.28,29 rRT-PCR has the advantage of avoiding the contamination problem during the procedure, which is a drawback of nested RT-PCR.30 Nested RT-PCR comprises two consecutive rounds of PCR amplification to improve sensitivity. Generally, those two PCR amplification process is performed in two tubes, which requires manual handling of amplicons. Also, to detect and prevent the contamination of complementary DNA (cDNA), both positive and negative controls are required in each PCR rounds. Hence, the cross-contamination would occur between primary and secondary PCR. After the secondary PCR is finished, it is needed to transfer the nested PCR products to the agarose gel electrophoresis to detect the products. This process also increases the risk of contamination. However, in the case of rRT-PCR, the risk of contamination is low because both the PCR and detection of the products are performed in a sealed system without handling of amplicons. Several studies have established the sensitivity and specificity of rRT-PCR for the detection of BDV genes.31,32 Hence, we used rRT-PCR to investigate BDV infection in psychiatric patients. To our knowledge, it is the first study to examine BDV RNA in psychiatric patients by rRT-PCR. Considering some evidence indicating discrepancies between serologic studies and rRT-PCR results,33 we used both an indirect immunofluorescence antibody (IFA) test and rRT-PCR to compare the results of the two methods. This study investigated BDV RNA and BDV antibody using rRT-PCR and indirect IFA test from peripheral blood mononuclear cells of psychiatric patients in Korea.



During January 2004 and December 2007, 198 psychiatric patients and 60 normal controls were recruited. All the patients were newly admitted in closed wards of the Department of Psychiatry, Ansan Hospital. Of the 198 patients, 98 patients had major depressive disorder, 60 had schizophrenia, and 40 had bipolar disorder. All the patients were interviewed by structured diagnostic criteria categorized according to the criteria of the fourth edition of the American Psychiatric Association.34 All the patients had active symptoms at the time of enrollment. Sixty normal controls were randomly selected among healthy individuals visiting the same hospital for regular health screens. All the patients and controls gave informed consent after a complete description of the study. The study protocol was approved by the Ethics Committee of Korea University.

Preparation of peripheral blood mononuclear cells

A sample of fasting blood (20 mL) was drawn from each of the 198 patients and 60 controls. Preparation of peripheral blood mononuclear cells (PBMCs) were isolated from anticoagulant-treated blood by Ficoll-hypaque gradient centrifugation. Total RNA was extracted from PBMCs using RNAzol (Gibco/BRL, Gaithersburg, MD, USA).

Serological detection of Borna disease virus infection with an indirect immunofluorescent antibody test

An indirect IFA test was conducted according to the method previously described.18 The Madine Darby canine kidney (MDCK) cell line and MDCK cell line persistently infected with BDV (MDCK-BDV)35 cultured for five days with Dulbecco's Modified Eagle Medium (DMEM)(Gibco/BRL, Germany) supplemented with 10% fetal bovine serum (FBS)(Gibco/BRL, Germany) were trypsinized, suspended in phosphate buffered saline (PBS), spotted onto Teflon-coated 10-well slides, and air-dried in room temperature. Cells on the 10-well antigen slide were fixed with anhydrous acetone at -20℃ for 7 minutes and dried. Human and horse serum samples diluted in PBS as 1 : 32 were treated to the MDCK cell and MDCK-BDV cell on the antigen slide, and the slide was incubated in a humidity chamber at 37℃ for 30 minutes. After three washes with PBS, Fluorescein isothiocyanate (FITC) conjugated anti-human immunoglobulin goat IgG (MP Biomedicals Inc., USA) was added to each well, and the slide was incubated in the humidity chamber at 37℃ for 30 minutes. The slides were mounted with glycine-buffered glycerol under cover slips and examined for a characteristic cytoplasmic fluorescent pattern with a fluorescence microscope.

Genetic detection of viral genomic RNA with real-time reverse transcription-polymerase chain reaction

Real-time quantitative RT-PCR for nucleoprotein (p40) and phosphoprotein (p24) genes of BDV was performed to detect the RNA genome of BDV in PBMCs. TaqMan probes were labeled with 6-carboxy fluorescein (FAM) as the 5' fluorescent reporter and tetramethylrhodamine (TAMRA) as the 3' quencher. The primers and probes were made as follows, in accordance with the previous report:36

  • p40 forward primer: 5'-TTTCATACAGTAACGCCCAGCC-3'

  • p40 reward primer: 5'-GGCGTCGACAGGTAAGATTCA-3'


  • p24 forward primer: 5'-ATGCATTGACCCAACCGGTA-3'

  • p24 reward primer: 5'-ATCATTCGATAGCTGCTCCCTTC-3'


For the construction of the quantitative standard, the p40 and p24 genes were amplified by RT-PCR and cloned to pGEM-T Easy vector system (Promega, USA). PCR primers were made as follows:





Cloned p40 and p24 genes were transcribed to RNA using the MEGAscript T7 transcription kit (Ambion Inc., USA) in accordance with the manufacturer's instructions. A reverse transcription reaction was performed on the final 1×1010 copies of cDNA per 1 µL using the p40-F and p24-F primers. The cDNA mixtures were diluted by the 10-fold dilution method until 1×103 copies of cDNA per 1 µL were obtained. The real-time PCR reaction mixture consisted of the Taqman Universal PCR Master Mix (Applied Biosystems, USA), as recommended in the manufacturer's instructions. The real-time PCR reaction mixtures were incubated for 10 minutes at 95℃, and 40 cycles of amplification were performed using the ABI PRISM 7000 Sequence Detection System (Applied Biosystems, USA), each cycle consisting of a denaturation step (15 seconds at 95℃) and an annealing-elongation step (1 minute at 60℃). The threshold cycle (Ct) values, or the number of cycles for fluorescence to reach clearly detectable levels, a value greater than 40 was regarded as a negative result (Table 2).


Threshold cycle (Ct) values in rRT-PCR assay

Statistical analysis

To analyze the demographic data, a two-tailed t-test was used for continuous covariates. For discrete covariates, a chi-square test was used. The null hypothesis was rejected at p<0.05. The statistical package used for the analysis was Statistical Package for Social Science (SPSS; SPSS Inc, Chicago, IL, USA) 11.01.


Demographic data

Normal controls and psychiatric patients were compared on age and sex (Table 3). There was no significant difference in the male/female ratio between the controls and patients groups. However, the controls were significantly older than the patients (p=0.009).


Demographic data

Immunofluorescence antibody and real-time reverse transcriptase polymerase chain reaction

p24 and p40 RNA were not detected by rRT-PCR in the controls and patients. In addition, the BDV antibody was not detected by the IFA in either group.


In this study, we failed to detect the BDV antibody or RNA from peripheral blood mononuclear cells (PBMC) in psychiatric patients. Due to no evidence of BDV infection, we could not compare the results of the IFA and rRT-PCR. Including our previous studies,37,38 there have been several studies suggesting a dissociation between BDV and human psychiatric diseases.33,39-42

There are several possible reasons for these controversial results. First, positive results might have been induced by laboratory artifacts such as contamination. As mentioned before, nested RT-PCR is prone to contamination during procedures. It has been suggested that BDV sequences found in human samples are very similar to the laboratory strains.43,44 Recently, in a meta-analytic study, Dürrwald et al.45 suggested that all the studies with BDV-positive results by nested RT-PCR might have used contaminated samples. The advantage of our study is that we used rRT-PCR which is the preferred methods to prevent cross-contamination. Because rRT-PCR could also have the possible risk of contamination, we specially paid attention to keep all the equipments cleaned and decontaminated. However, several studies have demonstrated that RT-PCR positive results were more frequent in patients than in controls.46,47 The findings suggest that contamination cannot fully explain the discrepancies in conflict RT-PCR results. With regard to the seroepidemiological study, the low avidity of human antibodies against BDV antigens compared to the high avidity of infected animal antibodies has raised the possibility that seroprevalence of BDV in humans might be the result of cross-reactivity.48 Second, the negative results might have been derived from the area in which the BDV infection of the animal is not endemic. The fact that we have consistently failed to demonstrate BDV infection in Korean psychiatric patients supports this notion.37,38 However, the conflicting results regarding BDV infection cannot be attributed only to geographic factors. It has been reported that BDV is not associated with psychiatric patients in Kyushu island in Japan, a known endemic area of BDV infection.8,42,49 However, there have been two BDV-positive reports in Brazil, which has not been known to be an endemic BDV infection area.23,24 Third, the pathogenesis and symptoms of BDV infection in humans would be different from the infection in animals. Recently, Matsunage et al.50 have suggested that human infection of BDV would be asymptomatic and non-pathogenic.

In conclusion, this study supports our previous results that BDV is not associated with psychiatric patients in Korea. However, it remains controversial whether BDV infection is associated with human psychiatric diseases. To clarify the presence of BDV in psychiatric patients, subsequent studies with novel diagnostic tools are needed.


Funding for this study was provided by a grant from the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (A040042).


1. Yolken RH, Torrey EF. Viruses, schizophrenia, and bipolar disorder. Clin Microbiol Rev 1995;8:131–145. 7704891.
2. de la Torre JC. Molecular biology of borna disease virus: prototype of a new group of animal viruses. J Virol 1994;68:7669–7675. 7966555.
3. Kohno T, Goto T, Takasaki T, Morita C, Nakaya T, Ikuta K, et al. Fine structure and morphogenesis of Borna disease virus. J Virol 1999;73:760–766. 9847384.
4. Gonzalez-Dunia D, Sauder C, de la Torre JC. Borna disease virus and the brain. Brain Res Bull 1997;44:647–664. 9421127.
5. Okamoto M, Furuoka H, Hagiwara K, Kamitani W, Kirisawa R, Ikuta K, et al. Borna disease in a heifer in Japan. Vet Rec 2002;150:16–18. 11817858.
6. Richt JA, Pfeuffer I, Christ M, Frese K, Bechter K, Herzog S. Borna disease virus infection in animals and humans. Emerg Infect Dis 1997;3:343–352. 9284379.
7. Rott R, Becht H. Natural and experimental Borna disease in animals. Curr Top Microbiol Immunol 1995;190:17–30. 7789148.
8. Watanabe Y, Yanai H, Ohtaki N, Ikuta K, Tomonaga K. Prevalence of Borna disease virus antibodies in healthy Japanese black cattle in Kyushu. J Vet Med Sci 2006;68:171–174. 16520541.
9. Briese T, Hornig M, Lipkin WI. Bornavirus immunopathogenesis in rodents: models for human neurological diseases. J Neurovirol 1999;5:604–612. 10602401.
10. Pletnikov MV, Moran TH, Carbone KM. Borna disease virus infection of the neonatal rat: developmental brain injury model of autism spectrum disorders. Front Biosci 2002;7:d593–d607. 11861216.
11. Lancaster K, Dietz DM, Moran TH, Pletnikov MV. Abnormal social behaviors in young and adult rats neonatally infected with Borna disease virus. Behav Brain Res 2007;176:141–148. 16860408.
12. Bautista JR, Rubin SA, Moran TH, Schwartz GJ, Carbone KM. Developmental injury to the cerebellum following perinatal Borna disease virus infection. Brain Res Dev Brain Res 1995;90:45–53.
13. Nakamura Y, Takahashi H, Shoya Y, Nakaya T, Watanabe M, Tomonaga K, et al. Isolation of Borna disease virus from human brain tissue. J Virol 2000;74:4601–4611. 10775596.
14. Hornig M, Solbrig M, Horscroft N, Weissenböck H, Lipkin WI. Borna disease virus infection of adult and neonatal rats: models for neuropsychiatric disease. Curr Top Microbiol Immunol 2001;253:157–177. 11417134.
15. Ovanesov MV, Moldovan K, Smith K, Vogel MW, Pletnikov MV. Persistent Borna Disease Virus (BDV) infection activates microglia prior to a detectable loss of granule cells in the hippocampus. J Neuroinflammation 2008;5:16. 18489759.
16. Volmer R, Prat CM, Le Masson G, Garenne A, Gonzalez-Dunia D. Borna disease virus infection impairs synaptic plasticity. J Virol 2007;81:8833–8837. 17553893.
17. Williams BL, Lipkin WI. Endoplasmic reticulum stress and neurode-generation in rats neonatally infected with borna disease virus. J Virol 2006;80:8613–8626. 16912310.
18. Rott R, Herzog S, Fleischer B, Winokur A, Amsterdam J, Dyson W, et al. Detection of serum antibodies to Borna disease virus in patients with psychiatric disorders. Science 1985;228:755–756. 3922055.
19. Bode L, Zimmermann W, Ferszt R, Steinbach F, Ludwig H. Borna disease virus genome transcribed and expressed in psychiatric patients. Nat Med 1995;1:232–236. 7585039.
20. Vahlenkamp TW, Enbergs HK, Müller H. Experimental and natural borna disease virus infections: presence of viral RNA in cells of the peripheral blood. Vet Microbiol 2000;76:229–244. 10973698.
21. Lebain P, Vabret A, Freymuth F, Brazo P, Chabot B, Dollfus S, et al. Borna disease virus and psychiatric disorders. Schizophr Res 2002;57:303–305. 12223262.
22. Kinnunen PM, Billich C, Ek-Kommonen C, Henttonen H, Kallio RK, Niemimaa J, et al. Serological evidence for Borna disease virus infection in humans, wild rodents and other vertebrates in Finland. J Clin Virol 2007;38:64–69. 17129759.
23. Miranda HC, Nunes SO, Calvo ES, Suzart S, Itano EN, Watanabe MA. Detection of Borna disease virus p24 RNA in peripheral blood cells from Brazilian mood and psychotic disorder patients. J Affect Disord 2006;90:43–47. 16324750.
24. Nunes SO, Itano EN, Amarante MK, Reiche EM, Miranda HC, de Oliveira CE, et al. RNA from Borna disease virus in patients with schizophrenia, schizoaffective patients, and in their biological relatives. J Clin Lab Anal 2008;22:314–320. 18623121.
25. Rybakowski F, Sawada T, Yamaguchi K. Borna disease virus-reactive antibodies and recent-onset psychiatric disorders. Eur Psychiatry 2001;16:191–192. 11353599.
26. Terayama H, Nishino Y, Kishi M, Ikuta K, Itoh M, Iwahashi K. Detection of anti-Borna Disease Virus (BDV) antibodies from patients with schizophrenia and mood disorders in Japan. Psychiatry Res 2003;120:201–206. 14527651.
27. Schwemmle M. Borna disease virus infection in psychiatric patients: are we on the right track? Lancet Infect Dis 2001;1:46–52. 11871411.
28. Espy MJ, Uhl JR, Sloan LM, Buckwalter SP, Jones MF, Vetter EA, et al. Real-time PCR in clinical microbiology: applications for routine laboratory testing. Clin Microbiol Rev 2006;19:165–256. 16418529.
29. Watzinger F, Ebner K, Lion T. Detection and monitoring of virus infections by real-time PCR. Mol Aspects Med 2006;27:254–298. 16481036.
30. Sorg I, Metzler A. Detection of Borna disease virus RNA in formalin-fixed, paraffin-embedded brain tissues by nested PCR. J Clin Microbiol 1995;33:821–823. 7790444.
31. Wensman JJ, Thorén P, Hakhverdyan M, Belák S, Berg M. Development of a real-time RT-PCR assay for improved detection of Borna disease virus. J Virol Methods 2007;143:1–10. 17376545.
32. Schindler AR, Vögtlin A, Hilbe M, Puorger M, Zlinszky K, Ackermann M, et al. Reverse transcription real-time PCR assays for detection and quantification of Borna disease virus in diseased hosts. Mol Cell Probes 2007;21:47–55. 17014984.
33. Wolff T, Heins G, Pauli G, Burger R, Kurth R. Failure to detect Borna disease virus antigen and RNA in human blood. J Clin Virol 2006;36:309–311. 16822717.
34. APA. Diagnostic and statistical manual of mental disorders IV 1994. Washington, D.C.: American Psychiatric Association.
35. Herzog S, Rott R. Replication of Borna disease virus in cell cultures. Med Microbiol Immunol 1980;168:153–158. 6772932.
36. Watanabe M, Lee BJ, Kamitani W, Kobayashi T, Taniyama H, Tomonaga K, et al. Neurological diseases and viral dynamics in the brains of neonatally borna disease virus-infected gerbils. Virology 2001;282:65–76. 11259191.
37. Kim YK, Kim SH, Han CS, Lee HJ, Kim HS, Yoon SC, et al. Borna disease virus and deficit schizophrenia. Acta Neuropsychiatr 2003;15:262–265.
38. Kim YK, Kim SH, Choi SH, Ko YH, Kim L, Lee MS, et al. Failure to demonstrate Borna disease virus genome in peripheral blood mononuclear cells from psychiatric patients in Korea. J Neurovirol 1999;5:196–199. 10321984.
39. Bachmann S, Caplazi P, Fischer M, Ehrensperger F, Cone RW. Lack of association between Borna disease virus infection and neurological disorders among HIV-infected individuals. J Neurovirol 1999;5:190–195. 10321983.
40. Richt JA, Alexander RC, Herzog S, Hooper DC, Kean R, Spitsin S, et al. Failure to detect Borna disease virus infection in peripheral blood leukocytes from humans with psychiatric disorders. J Neurovirol 1997;3:174–178. 9111180.
41. Lieb K, Hallensleben W, Czygan M, Stitz L, Staeheli P. The Bornavirus Study Group. No Borna disease virus-specific RNA detected in blood from psychiatric patients in different regions of Germany. Lancet 1997;350:1002. 9329518.
42. Tsuji K, Toyomasu K, Imamura Y, Maeda H, Toyoda T. No association of borna disease virus with psychiatric disorders among patients in northern Kyushu, Japan. J Med Virol 2000;61:336–340. 10861642.
43. Staeheli P, Sauder C, Hausmann J, Ehrensperger F, Schwemmle M. Epidemiology of Borna disease virus. J Gen Virol 2000;81:2123–2135. 10950968.
44. Schwemmle M, Jehle C, Formella S, Staeheli P. Sequence similarities between human bornavirus isolates and laboratory strains question human origin. Lancet 1999;354:1973–1974. 10622306.
45. Dürrwald R, Kolodziejek J, Herzog S, Nowotny N. Meta-analysis of putative human bornavirus sequences fails to provide evidence implicating Borna disease virus in mental illness. Rev Med Virol 2007;17:181–203. 17342788.
46. Sauder C, Müller A, Cubitt B, Mayer J, Steinmetz J, Trabert W, et al. 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 1996;70:7713–7724. 8892892.
47. Igata-Yi R, Yamaguchi K, Yoshiki K, Takemoto S, Yamasaki H, Matsuoka M, et al. Borna disease virus and the consumption of raw horse meat. Nat Med 1996;2:948–949. 8782439.
48. Allmang U, Hofer M, Herzog S, Bechter K, Staeheli P. Low avidity of human serum antibodies for Borna disease virus antigens questions their diagnostic value. Mol Psychiatry 2001;6:329–333. 11326304.
49. Inoue Y, Yamaguchi K, Sawada T, Rivero JC, Horii Y. Demonstration of continuously seropositive population against Borna disease virus in Misaki feral horses, a Japanese strain: a four-year follow-up study from 1998 to 2001. J Vet Med Sci 2002;64:445–448. 12069079.
50. Matsunaga H, Tanaka S, Fukumori A, Tomonaga K, Ikuta K, Amino N, et al. Isotype analysis of human anti-Borna disease virus antibodies in Japanese psychiatric and general population. J Clin Virol 2008;43:317–322. 18786855.
51. Kishi M, Nakaya T, Nakamura Y, Kakinuma M, Takahashi TA, Sekiguchi S, et al. Prevalence of Borna disease virus RNA in peripheral blood mononuclear cells from blood donors. Med Microbiol Immunol 1995;184:135–138. 8577314.
52. Kishi M, Nakaya T, Nakamura Y, Zhong Q, Ikeda K, Senjo M, et al. Demonstration of human Borna disease virus RNA in human peripheral blood mononuclear cells. FEBS Lett 1995;364:293–297. 7538936.
53. Nakaya T, Takahashi H, Nakamura Y, Asahi S, Tobiume M, Kuratsune H, et al. Demonstration of Borna disease virus RNA in peripheral blood mononuclear cells derived from Japanese patients with chronic fatigue syndrome. FEBS Lett 1996;378:145–149. 8549821.
54. Iwahashi K, Watanabe M, Nakamura K, Suwaki H, Nakaya T, Nakamura Y, et al. Clinical investigation of the relationship between Borna disease virus (BDV) infection and schizophrenia in 67 patients in Japan. Acta Psychiatr Scand 1997;96:412–415. 9421336.
55. Kubo K, Fujiyoshi T, Yokoyama MM, Kamei K, Richt JA, Kitze B, et al. Lack of association of Borna disease virus and human T-cell leukemia virus type 1 infections with psychiatric disorders among Japanese patients. Clin Diagn Lab Immunol 1997;4:189–194. 9067654.
56. Takahashi H, Nakaya T, Nakamura Y, Asahi S, Onishi Y, Ikebuchi K, et al. Higher prevalence of Borna disease virus infection in blood donors living near thoroughbred horse farms. J Med Virol 1997;52:330–335. 9210045.
57. Iwata Y, Takahashi K, Peng X, Fukuda K, Ohno K, Ogawa T, et al. Detection and sequence analysis of borna disease virus p24 RNA from peripheral blood mononuclear cells of patients with mood disorders or schizophrenia and of blood donors. J Virol 1998;72:10044–10049. 9811743.
58. Planz O, Rentzsch C, Batra A, Rziha HJ, Stitz L. Persistence of Borna disease virus-specific nucleic acid in blood of psychiatric patient. Lancet 1998;352:623. 9746029.
59. Planz O, Rentzsch C, Batra A, Winkler T, Büttner M, Rziha HJ, et al. Pathogenesis of borna disease virus: granulocyte fractions of psychiatric patients harbor infectious virus in the absence of antiviral antibodies. J Virol 1999;73:6251–6256. 10400715.
60. Chen CH, Chiu YL, Shaw CK, Tsai MT, Hwang AL, Hsiao KJ. Detection of Borna disease virus RNA from peripheral blood cells in schizophrenic patients and mental health workers. Mol Psychiatry 1999;4:566–571. 10578239.
61. Nakaya T, Takahashi H, Nakamur Y, Kuratsune H, Kitani T, Machii T, et al. Borna disease virus infection in two family clusters of patients with chronic fatigue syndrome. Microbiol Immunol 1999;43:679–689. 10529109.
62. Evengård B, Briese T, Lindh G, Lee S, Lipkin WI. Absence of evidence of Borna disease virus infection in Swedish patients with Chronic Fatigue Syndrome. J Neurovirol 1999;5:495–499. 10568886.
63. Nowotny N, Kolodziejek J. Demonstration of borna disease virus nucleic acid in a patient with chronic fatigue syndrome. J Infect Dis 2000;181:1860–1862. 10823802.
64. Fukuda K, Takahashi K, Iwata Y, Mori N, Gonda K, Ogawa T, et al. Immunological and PCR analyses for Borna disease virus in psychiatric patients and blood donors in Japan. J Clin Microbiol 2001;39:419–429. 11158085.
65. Kim YK, Kim SH, Han CS, Lee HJ, Kim HS, Yoon SC, et al. Borna disease virus and deficit schizophrenia. Acta Neuropsychiatr 2003;15:262–265.
66. Li Q, Wang Z, Zhu D, Xu M, Chen X, Peng D, et al. Detection and analysis of Borna disease virus in Chinese patients with neurological disorders. Eur J Neurol 2009;16:399–403. 19364367.
67. Lieb K, Staeheli P. Borna disease virus--does it infect humans and cause psychiatric disorders? J Clin Virol 2001;21:119–127. 11378492.

Article information Continued


Published studies of BDV detection by RT-PCR in neuropsychiatric samples of human peripheral blood


This Table is modified from <Table 1, studies aimed at detecting BDV by RT-PCR in samples of human peripheral blood>67. BDV: Borna disease virus, RT-PCR: reverse transcriptase polymerase chain reaction, PBMCs: peripheral blood mononuclear cells


Threshold cycle (Ct) values in rRT-PCR assay


Ct value: threshold cycle. rRT-PCR: real time reverse transcriptase polymerase chain reaction


Demographic data