Tag: Borna disease

Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis

Abstract:

Background: Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many studies have confirmed the symptoms similar to ME/CFS in the recovered individuals. To investigate the virus-related etiopathogenesis of ME/CFS, we conducted a systematic assessment of viral infection frequency in ME/CFS patients.

Methods: We conducted a comprehensive search of PubMed and the Cochrane Library from their inception through December 31, 2022, using selection criteria of viral infection prevalence in ME/CFS patients and controls. Subsequently, we performed a meta-analysis to assess the extent of viral infections’ contribution to ME/CFS by comparing the odds ratio between ME/CFS patients and controls (healthy and/or diseased).

Results: Finally, 64 studies met our eligibility criteria regarding 18 species of viruses, including a total of 4971 ME/CFS patients and 9221 control subjects. The participants included healthy subjects and individuals with one of 10 diseases, such as multiple sclerosis or fibromyalgia. Two DNA viruses (human herpes virus (HHV)-7 and parvovirus B19, including their co-infection) and 3 RNA viruses (borna disease virus (BDV), enterovirus and coxsackie B virus) showed odds ratios greater than 2.0 compared with healthy and/or diseased subjects. Specifically, BDV exceeded the cutoff with an odds ratio of ≥ 3.47 (indicating a “moderate association” by Cohen’s d test) compared to both healthy and diseased controls.

Conclusion: This study comprehensively evaluated the risk of viral infections associated with ME/CFS, and identified BDV. These results provide valuable reference data for future studies investigating the role of viruses in the causation of ME/CFS.

Source: Hwang, JH., Lee, JS., Oh, HM. et al. Evaluation of viral infection as an etiology of ME/CFS: a systematic review and meta-analysis. J Transl Med 21, 763 (2023). https://doi.org/10.1186/s12967-023-04635-0 https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04635-0 (Full text)

Clinical characteristics of patients with chronic fatigue syndrome: analysis of 82 cases

Abstract:

OBJECTIVE: To analyze the clinical characteristics of Chinese patients suffering from chronic fatigue syndrome (CFS) and provide clinical and laboratory evidence for the study of its etiology and treatment.

METHODS: 82 patients with CFS diagnosed based on the CDC criteria 1994 were recruited. History was collected, and physical examination was made. SCL-90 and memory test were used, and Hamilton Anxiety Rating Scale was used to those showing depression and/or anxiety. Laboratory examination, including examination of electrolytes, blood sugar, creatinine, bilirubin, alkaline phosphatase, alanine trasaminase, etc, was conducted. Western blotting was used to detect the protein-24 of Borna disease virus (BDV) in the plasma of 61 patients and 73 healthy controls. High-pressure chromatography was conducted to detect n-6 fatty acids on the membrane of erythrocytes of 42 patients and 37 healthy controls. Plasma L-carnitine in 61 patients and 73 healthy controls was detected by zymological analysis. In different examinations sex and age-matched controls were used.

RESULTS: Most of the patients were 21 approximately 50 years old (74/82, 90.24%). No gender difference was found. The patients usually had 4 approximately 6 symptoms besides distinctive fatigue. Descent of remembrance and/or attention was the most conspicuous accompanying symptoms (69/82, 84.15%). Abnormalities in SCL-90 scores were present in 57 patients (69.51%), e.g, somatization existed most commonly (32/82, 39.02%), and anxiety and depression were 20.73% (17/82) and 18.29% (15/82) respectively. The prevalence of anti-BDV-p24 antibody was 20.73% (17/82), significantly higher than that of the controls (0%, chi(2) = 6.673, P = 0.010). The arachidonic acid level was significantly lower in the CFS group than in the controls (P > 0.05) and there were no differences in linoleic acid and ETA (both P > 0.05). The level of L-carnitine was 6.4336 +/- 3.4225, significantly lower than that of the control group (7.6666 +/- 3.5819, t = 2.025, P = 0.045) and the L-carnitine level was increased 2 weeks after supplementary treatment, together with improvement of symptoms.

CONCLUSION: Most of the CFS patients are young and middle-aged. Descent of reorganization is common in these patients. Psychological abnormalities exist in most patients. Some patients are infected with BDV, some with deficiency of nutrition and/or abnormality of energy metabolism.

 

Source: Li YJ, Wang DX, Bai XL, Chen J, Liu ZD, Feng ZJ, Zhao YM. Clinical characteristics of patients with chronic fatigue syndrome: analysis of 82 cases. Zhonghua Yi Xue Za Zhi. 2005 Mar 16;85(10):701-4. [Article in Chinese] http://www.ncbi.nlm.nih.gov/pubmed/15932738

 

Search for Borna disease virus in Danish fibromyalgia patients

Abstract:

OBJECTIVE: The purpose of this study was to look for Borna disease virus (BDV) in 18 patients with acute onset of fibromyalgia (FMS) following a “flu-like” episode. BDV is a neurotropic RNA virus affecting horses and sheep. Infections in animals have been reported to cause immune mediated disease characterized by abnormalities in behavior. A possible link between BDV and neuropsychiatric diseases in man has been described, and lately a connection to chronic fatigue syndrome (CFS) has been suggested.

METHODS: A BDV-specific nested PCR (RT-PCR) was performed on serum and spinal fluid.

RESULTS: The BDV genome was not detected in any of the FMS cases.

CONCLUSION: Although BDV was not demonstrated in spinal fluid or serum from the tested patients with FMS, we believe that it is important to report our results, since FMS can exhibit many manifestations in common with CFS. Possible reasons for the discrepant findings are discussed.

 

Source: Wittrup IH, Christensen LS, Jensen B, Danneskiold-Samsee B, Bliddal H, Wiik A. Search for Borna disease virus in Danish fibromyalgia patients. Scand J Rheumatol. 2000;29(6):387-90. http://www.ncbi.nlm.nih.gov/pubmed/11132208

 

Demonstration of borna disease virus nucleic acid in a patient with chronic fatigue syndrome

Comment on: Borna disease virus in human brains with a rare form of hippocampal degeneration but not in brains of patients with common neuropsychiatric disorders. [J Infect Dis. 1999]

 

To the Editor

Czygan et al. [1]reported the detection of Borna disease virus (BDV) nucleic acid in 3 cases of a rare form of hippocampal degeneration, whereas the brains of patients with other neuropsychiatric disorders tested negative for BDV. Chronic fatigue syndrome (CFS) is another, more frequently diagnosed neuropsychiatric disease that is associated with BDV infection. However, the published findings are highly controversial. Nakaya et al. [2, 3] and Kitani et al. [4] showed both BDV-specific antibodies and RNA in a high percentage of Japanese patients with CFS. Bode et al. [5]isolated BDV from peripheral blood mononuclear cells (PBMC) of an American patient with CFS; however, in an earlier publication, Bode et al. [6], as well as Evengård et al. [7] and Yamaguchi et al. [8] in recent publications, did not find serologie evidence for BDV in patients with CFS. A possible explanation for the controversial results is that the term “chronic fatigue syndrome” probably includes several similar clinical conditions that may have different etiologies. In the study by Czygan et al. [1], brain tissue samples from patients who had CFS were not included. Unfortunately, none of the BDV sequences of the CFS cases mentioned above are available in the GenBank database.

You can read the rest of this comment here: http://jid.oxfordjournals.org/content/181/5/1860.long

 

Source: Nowotny N, Kolodziejek J. Demonstration of borna disease virus nucleic acid in a patient with chronic fatigue syndrome. J Infect Dis. 2000 May;181(5):1860-2. http://jid.oxfordjournals.org/content/181/5/1860.long (Full article)

 

Absence of evidence of Borna disease virus infection in Swedish patients with Chronic Fatigue Syndrome

Abstract:

Chronic Fatigue Syndrome (CFS) is characterized by debilitating fatigue, somatic symptoms and cognitive impairment. An infectious basis has been proposed; candidate agents include enteroviruses, herpesviruses, retroviruses and Borna disease virus (BDV), a novel neurotropic virus associated with neuropsychiatric disorders.

Sera and peripheral blood mononuclear cells (PBMC) from Swedish CFS patients were assayed for evidence of infection using ELISA and Western immunoblot for detection of antibodies to BDV proteins N, P and gp18; and using nested reverse transcriptase polymerase chain reaction (RT-PCR) for detection of BDV N- and P-gene transcripts. No specific immunoreactivity to BDV proteins was found in sera from 169 patients or 62 controls.

No BDV N- or P-gene transcripts were found through RT-PCR analysis of PBMC from 18 patients with severe CFS. These results do not support a role for BDV in pathogenesis of CFS.

 

Source: 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 Oct;5(5):495-9. http://www.ncbi.nlm.nih.gov/pubmed/10568886

 

Borna disease virus infection in two family clusters of patients with chronic fatigue syndrome

Abstract:

A high rate of Borna disease virus (BDV) infection has been demonstrated in patients with chronic fatigue syndrome (CFS). Herein, we focused on BDV infection in two family clusters of patients with CFS: a father, mother, two sons and one daughter (family #1); and a father, mother, two daughters and one son (family #2).

All members, except for the elder son in family #1 and the father and son in family #2, were diagnosed with CFS. The results supported that all the family members with CFS were infected with BDV, as evidenced by the presence of antibodies to viral p40, p24 and/or gp18 and BDV p24 RNA in peripheral blood mononuclear cells.

The healthy members, except for the father of family #2 who was positive for antibody to p24, were all negative by both assays. Follow-up studies in family #1 continued to reveal BDV antibodies and BDV RNA, except in the mother, who lost the RNA upon slight recovery from the disease.

 

Source: Nakaya T, Takahashi H, Nakamur Y, Kuratsune H, Kitani T, Machii T, Yamanishi K, Ikuta K. Borna disease virus infection in two family clusters of patients with chronic fatigue syndrome. Microbiol Immunol. 1999;43(7):679-89. http://onlinelibrary.wiley.com/doi/10.1111/j.1348-0421.1999.tb02456.x/full (Full article)

 

Detection of borna disease virus-reactive antibodies from patients with psychiatric disorders and from horses by electrochemiluminescence immunoassay

Abstract:

The prevalence of Borna disease virus (BDV)-specific antibodies among patients with psychiatric disorders and healthy individuals has varied in several reports using several different serological assay methods. A reliable and specific method for anti-BDV antibodies needs to be developed to clarify the pathological significance of BDV infections in humans.

We developed a new electrochemiluminescence immunoassay (ECLIA) for the antibody to BDV that uses two recombinant proteins of BDV, p40 and p24 (full length). Using this ECLIA, we examined 3,476 serum samples from humans with various diseases and 917 sera from blood donors in Japan for the presence of anti-BDV antibodies.

By ECLIA, 26 (3.08%) of 845 schizophrenia patients and 9 (3.59%) of 251 patients with mood disorders were seropositive for BDV. Among 323 patients with other psychiatric diseases, 114 with neurological diseases, 75 with chronic fatigue syndrome, 85 human immunodeficiency virus-infected patients, 50 with autoimmune diseases including rheumatoid arthritis and systemic lupus erythematosis and 17 with leprosy, there was no positive case except one case each with alcohol addiction, AIDS, and dementia.

Although 19 (1.36%) of 1,393 patients with various ocular diseases, 10 (1.09%) of 917 blood donors, and 3 (4.55%) of 66 multitransfused patients were seropositive for BDV-specific antigen, high levels of seroprevalence in schizophrenia patients and young patients (16 to 59 years old) with mood disorders were statistically significant.

The immunoreactivity of seropositive sera could be verified for specificity by blocking with soluble p40 and/or p24 recombinant protein. Anti-p24 antibody was more frequent than p40 antibody in most cases, and in some psychotic patients antibody profiles showed only p40 antibody. Although serum positive for both p40 and p24 antibodies was not found in this study, the p40 ECLIA count in schizophrenia patients was higher than that of blood donors.

Furthermore, we examined 90 sera from Japanese feral horses. Antibody profiles of control human samples are similar to that of naturally BDV-infected feral horses. We concluded that BDV infection was associated in some way with psychiatric disorders.

 

Source: 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. Detection of borna disease virus-reactive antibodies from patients with psychiatric disorders and from horses by electrochemiluminescence immunoassay. Clin Diagn Lab Immunol. 1999 Sep;6(5):696-700. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC95757/ (Full article)

 

Demonstration on Borna disease virus in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS), a recently named heterogeneous disorder, is an illness of unknown etiology. The association between CFS and several viral infection has been suggested. Here, we centered on the possible link between CFS and Borna disease virus (BDV) infection.

BDV is a neurotropic, nonsegmented negative-strand (NNS) RNA virus. Recent epidemiological data have suggested that BDV may be closely associated with depression and schizophrenia in humans.

In Japanese patients with CFS, the prevalence of BDV infection was 34% (30/89) and 12% (7/57) by immunoblotting and PCR analysis, respectively. Furthermore, anti-BDV antibodies and BDV RNA were detected in a family cluster with CFS. These results suggested that this virus contributes to or initiates CFS, although the single etiologic role of BDV is unlikely.

 

Source: Nakaya T, Kuratsune H, Kitani T, Ikuta K. Demonstration on Borna disease virus in patients with chronic fatigue syndrome. Nihon Rinsho. 1997 Nov;55(11):3064-71. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/9396313

 

Lack of association of Borna disease virus and human T-cell leukemia virus type 1 infections with psychiatric disorders among Japanese patients

Abstract:

Borna disease virus (BDV) infection has been suspected to be a possible etiological factor in human psychiatric disorders and recently in chronic fatigue syndrome. Evidence of the correlation of BDV infection with these disorders remained unclear. Kagoshima is known to be one of the major areas in which human T-cell leukemia virus type 1 (HTLV-1) is endemic; this is the first isolated human retrovirus that causes adult T-cell leukemia with neurological symptoms. The present study aimed to clarify whether BDV and HTLV-1 infections are associated with psychiatric disorders among Japanese patients.

Subjects were 346 patients with psychiatric disorders (schizophrenia, 179; mood disorder, 123; and others, 44) and 70 healthy controls. Anti-BDV antibodies from plasma samples were screened by the indirect immunofluorescence (IF) method using BDV-infected MDCK cells. Results revealed that only three samples were found to be weakly positive for BDV in the IF assay and seronegative by Western blot (immunoblot) assay.

Furthermore, BDV-p24 related RNA in peripheral blood mononuclear cells from 106 of 346 psychiatric patients and 12 or 70 healthy controls by p24-reverse transcription PCR was examined. Two mood disorder patients were positive for BDV-p24 RNA but seronegative. To detect anti-HTLV-1 antibodies the plasma samples were screened by the particle agglutination method and no significant difference in seropositivity for anti-HTLV-1 antibody was found between the patients and healthy controls.

These results also suggested that there is a lack of association between BDV and HTLV-1 infections with psychiatric disorders among Japanese patients.

 

Source: Kubo K, Fujiyoshi T, Yokoyama MM, Kamei K, Richt JA, Kitze B, Herzog S, Takigawa M, Sonoda S. 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 Mar;4(2):189-94. http://www.ncbi.nlm.nih.gov/pubmed/9067654

 

Demonstration of Borna disease virus RNA in peripheral blood mononuclear cells derived from Japanese patients with chronic fatigue syndrome

Abstract:

CFS, a recently named heterogeneous disorder, is an illness of unknown etiology. The association of CFS with viral infections has been suggested. A common association between CFS and several viruses examined has not been confirmed.

Here, we centered on the possible link between CFS and BDV infection. By nested RT-PCR followed by hybridization, BDV RNA was demonstrated as a clear signal in PBMCs in 3 out of 25 CFS patients. The amplified cDNA fragments were cloned and sequenced. A total of 16 clones were studied. Intra-patients divergencies of the p24 were 2-9%, 3-20%, and 3-11% in the deduced amino acids. Inter-patient divergencies among the 16 clones were 3-24%. Antibodies to recombinant BDV p24 protein were detected in 6 CFS patients including one carrying BDV RNA.

Overall, these gave the prevalence of 32% (8/25) in Japanese CFS patients, suggesting that Japanese CFS is highly associated with active infection of BDV, or a related agent.

 

Source: Nakaya T, Takahashi H, Nakamura Y, Asahi S, Tobiume M, Kuratsune H, Kitani T, Yamanishi K, Ikuta K. Demonstration of Borna disease virus RNA in peripheral blood mononuclear cells derived from Japanese patients with chronic fatigue syndrome. FEBS Lett. 1996 Jan 8;378(2):145-9. http://onlinelibrary.wiley.com/doi/10.1016/0014-5793(95)01439-X/epdf (Full article)