Research reportDetection of Borna disease virus p24 RNA in peripheral blood cells from Brazilian mood and psychotic disorder patients
Introduction
Borna disease virus (BDV) is a neurotropic, enveloped, nonsegmented, negative single-stranded RNA virus and causes changes in brain function resulting in disturbed movement and behavior and may be associated with human psychiatric disorders (Amsterdam et al., 1985, Chen et al., 1999, Nakamura et al., 2000, Fukuda et al., 2001, Horning and Lipkin, 2001, Bode et al., 2001, Taieb et al., 2001).
The first report of spontaneous canine BDV in Japan (Okamoto et al., 2002) and epidemiological investigations have revealed that BDV may also infect humans (Bode et al., 1993, Waltrip et al., 1995).
The predilection of the virus for the limbic–hypothalamic region and production in some animals of a syndrome somewhat resembling human affective disorders suggested the possibility that BDV may be involved in some human affective disorders (Amsterdam et al., 1985).
BDV is highly neurotropic in natural and experimental hosts. It replicates in neurons and astrocytes without inducing cytopathic effects (Schneider et al., 2005). This virus infects the central nervous system (CNS) of many animal species and may cause behavioral disturbances reminiscent of autism, schizophrenia and mood disorders (Pletnikov et al., 2002, Tomonaga, 2004).
Bode et al. (1993) reported that the proportion of BDV antibody carriers was higher than 30% among patients with major depression. In addition, they also detected a high rate of viral RNA in peripheral blood mononuclear cells (PBMC) derived from psychiatric patients at a high rate by reverse transcriptase-polymerase chain reaction (RT-PCR) (Bode et al., 1995).
Molecular analysis has indicated that BDV genome consists of at least six open reading frames (ORFs). The ORFs encode nucleoprotein (p40), phosphoprotein (p24), transcriptional activator, matrix protein (gp18), envelope protein (p56), and a predicted RNA-dependent RNA polymerase (p180) in 5′ to 3′order (Schneider et al., 1997).
The second open reading frame (ORFII) codes for a 24 kDa protein (also known as p24), representing the putative phosphoprotein. In addition to the p24 protein, the second ORF also produces a 16 kDa protein by translation from the second in-frame AUG codon. This 16 kDa protein has been detected in BDV infected cultured cells and in brains of experimentally infected animals (Ikuta et al., 2002). Among these proteins, BDV-p40 and p24 are found as abundant proteins in BDV-infected brain cells of experimentally and naturally infected animals (Stitz et al., 2002).
Over the past few years, many reports of patients presenting psychiatric symptoms during viral infection were described. Mood disorder patients were reported to have BDV serum antibodies compared to samples from control group without psychotic and mood disorders (Taieb et al., 2001).
Most epidemiological studies employed RT-PCR or RT PCR-nested methodology to trace viral RNA in biological specimens. Thus, in the work we report the major findings regarding a RT-nested-PCR study of Borna disease virus p24-RNA in mood and psychotic disorder in Brazilian patients and healthy control individuals.
Section snippets
Subjects
The patients were adult outpatients of the Psychiatric Ambulatory of Londrina State University, Paraná, Brazil during the period from 2001 to 2003. Ethics Committee of Londrina State University approved the present study and the subjects signed a written informed consent to be included on the present study.
The subjects were 30 patients with psychiatric disorder from both genders, ranging in age from 18 to 68 years and 30 volunteers control subjects also from both genders ranging in age from 18
Results
There were no group differences in age, gender and ethnic group between patients and controls (Table 1).
A total of 30 psychiatric disorder patients were examined for BDV RNA in their blood peripheral cells. When the nested RT-PCR technique was applied for the detection of BDV related RNA, clear positive signals were detected in 33.33% (10/30) of the samples.
The mean duration of illness in mood and psychotic patients with p24 RNA of BDV was 25 (± 12.3) years and the median age was 43.77 (± 15.2)
Discussion
Nowadays, BDV has been observed in a variety of animal species including cats, dogs, cattle, sheep and horses. In addition, the potential role of BDV as a pathogen in human psychiatric diseases has increased the interest in the investigation of this virus and its pathogenenic pathways. Molecular biological analysis revealed important data, such as, type of genomic nucleic acid, genomic organization and BDV specific proteins.
In this study, we investigate the presence of p24 RNA of BDV in mood
Acknowledgements
We acknowledge the volunteers who made this study possible. This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES and Coordenadoria de Pós-Graduação Londrina State University-PROPPG-UEL.
References (33)
- et al.
Detection of Borna disease virus antigen and RNA in human autopsy brain samples from neuropsychiatric patients
Virology
(1996) - et al.
Detection of Borna disease virus genome in normal human brain tissue
Brain Res.
(1997) - et al.
High efficiency transformation of Escherichia Coli with plasmids
Gene
(1990) - et al.
Demonstration of human Borna disease virus RNA in human peripheral blood mononuclear cells
FEBS Lett.
(1995) - et al.
No Borna disease virus-specific RNA detected in blood from psychiatric patients from different regions of Germany
Lancet
(1997) - et al.
Borna disease in a dog in Japan
J. Comp. Pathol.
(2002) - et al.
Detection of anti-Borna disease virus (BDV) antibodies from patients with schizophrenia and mood disorders in Japan
Psychiatry Res.
(2003) Virus-induced neurobehavioral disorders: mechanisms and implications
Trends Mol. Med.
(2004)- et al.
Molecular and cellular biology of Borna disease virus infection
Microbes Infect.
(2002) - et al.
Borna disease virus. A possible etiologic factor in human Affective Disorders?
Arch. Gen. Psychiatry
(1985)
Human infections with Borna disease virus: seroprevalence in patients with chronic disease and healthy individuals
J. Med. Virol.
Borna disease virus infection and disorders in man
Arch. Virol.
Borna disease virus genome transcribed and expressed in psychiatric patients
Nat. Med.
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
Borna disease virus and the evidence for human pathogenicity: a systematic review
QJM
Detection of Borna disease virus RNA from peripheral blood cells in schizophrenic patients and mental health workers
Mol. Psychiatry
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