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

 

Evidence for enteroviral persistence in humans

Abstract:

We have sought evidence of enteroviral persistence in humans. Eight individuals with chronic fatigue syndrome (CFS) were positive for enteroviral sequences, detected by PCR in two serum samples taken at least 5 months apart. The nucleotide sequence of the 5′ non-translated region (bases 174-423) was determined for each amplicon.

Four individuals had virtually identical nucleotide sequences ( > 97%) in both samples. The sequence pairs also each had a unique shared pattern indicating that the virus had persisted. In one individual (HO), it was clear that there had been infection with two different enteroviruses.

In the remaining three individuals, the lack of unique shared features suggested that re-infection had occurred, rather than persistence. With the exception of HO, the sequences fell into a subgroup that is related to the Coxsackie B-like viruses.

 

Source: Galbraith DN, Nairn C, Clements GB. Evidence for enteroviral persistence in humans. J Gen Virol. 1997 Feb;78 ( Pt 2):307-12. http://www.ncbi.nlm.nih.gov/pubmed/9018051

 

Electron microscopic immunocytological profiles in chronic fatigue syndrome

Abstract:

Structures consistent in size, shape and character with various stages of a Lentivirus replicative cycle were observed by electron microscopy in 12-day peripheral-blood lymphocyte cultures from 10 of 17 Chronic Fatigue Syndrome patients and not in controls. Attempts to identify a lymphoid phenotype containing these structures by immunogold labelling failed and the results of reverse-transcriptase assay of culture supernatants were equivocal. The study was blind and case-controlled, patients being paired with age, sex and ethnically matched healthy volunteers. Prescreening of subjects included the common metabolic and immunological disorders, functional conditions and a virus-screen against hepatitis B and C, Epstein-Barr Virus, Cytomegalovirus and Human Immunodeficiency Virus.

 

Source: Holmes MJ, Diack DS, Easingwood RA, Cross JP, Carlisle B. Electron microscopic immunocytological profiles in chronic fatigue syndrome. J Psychiatr Res. 1997 Jan-Feb;31(1):115-22. http://www.ncbi.nlm.nih.gov/pubmed/9201653

 

Detection of RNA sequences in cultures of a stealth virus isolated from the cerebrospinal fluid of a health care worker with chronic fatigue syndrome. Case report

Abstract:

A cytopathic stealth virus was cultured from the cerebrospinal fluid of a nurse with chronic fatigue syndrome. Reverse transcriptase-polymerase chain reaction (RT-PCR) performed on the patient’s culture yielded positive results with primer sets based on sequences of a previously isolated African green monkey simian-cytomegalovirus-derived stealth virus. The same primer sets did not yield PCR products when tested directly on DNA extracted from the cultures. The findings lend support to the possibility of replicative RNA forms of certain stealth viruses and have important implications concerning the choice of therapy in this type of patient.

 

Source: Martin WJ. Detection of RNA sequences in cultures of a stealth virus isolated from the cerebrospinal fluid of a health care worker with chronic fatigue syndrome. Case report. Pathobiology. 1997;65(1):57-60. http://www.ncbi.nlm.nih.gov/pubmed/9200191

 

Changing epidemiology of Ross River virus disease in South Australia

Abstract:

OBJECTIVE: To investigate changes in epidemiology and symptoms of Ross River virus (RRV) disease in South Australia.

DESIGN: Longitudinal questionnaire-based survey of notified cases from one to 36 months after infection.

SUBJECTS: All patients with recent serologically confirmed RRV infection notified to the Communicable Disease Control Unit, South Australian Health Commission, between 1 October 1992 and 30 June 1993.

OUTCOME MEASURES: Sociodemographic data, source of infection, symptoms and ability to carry out daily activities (at onset of illness and at time of questionnaire, up to 36 months after infection), symptom duration, economic impact of the illness, cases recovery time, factors predictive of delayed recovery.

RESULTS: Information was obtained on the acute illness from 698 of the 821 subjects and at 15 months after infection from 436. At 15 months, 51% of respondents still had joint pain and 45% had persistent tiredness and lethargy. Other common symptoms included myalgia (34%), lymphadenopathy (25%), headache (23%) and depression (22%). These symptoms were still common 30 months after infection. Increasing age was the only statistically significant predictor of delayed recovery. Infections were acquired across the State, away from previously recognised RRV-endemic areas.

CONCLUSIONS: For many people, RRV disease is debilitating, with long term symptoms similar to those of chronic fatigue syndrome. The geographic range of the infection has expanded in SA.

Comment in:

The changing epidemiology of Ross River virus disease in South Australia. [Med J Aust. 1997]

Ross River virus disease and rheumatoid arthritis. [Med J Aust. 1997]

The changing epidemiology of Ross River virus disease in South Australia. [Med J Aust. 1997]

 

Source: Selden SM, Cameron AS. Changing epidemiology of Ross River virus disease in South Australia. Med J Aust. 1996 Sep 16;165(6):313-7. http://www.ncbi.nlm.nih.gov/pubmed/8862330

 

Are echoviruses still orphans?

Abstract:

A review of some of the outbreaks of disease caused by echoviruses demonstrates their ability to cause significant morbidity and mortality world-wide.

There are now 30 recognised echovirus serotypes; several of the original serotypes have been re-classified. More recently, echovirus 22 has been shown to have significant molecular differences from other types and unusual epidemiological features. Echovirus types 7, 11, 19 and 30 have been associated with significant outbreaks in neonatal units and echovirus types 9, 16 and 25 are more frequently associated with exanthem. Echovirus type 3, although relatively uncommon in the UK, was associated with large outbreaks in China.

Since the decline in poliomyelitis, the increase in reports of non-polio enteroviruses has revealed a corresponding increase in associated cases of myalgic encephalomyelitis and post-viral fatigue syndrome.

 

Source: Hill WM. Are echoviruses still orphans? Br J Biomed Sci. 1996 Sep;53(3):221-6. http://www.ncbi.nlm.nih.gov/pubmed/8914350

 

Viral serologies in patients with chronic fatigue and chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is an illness characterized by disabling fatigue associated with complaints of fevers, sore throat, myalgia, lymphadenopathy, sleep disturbances, neurocognitive difficulties, and depression. A striking feature of CFS is its sudden onset following an acute, presumably viral, illness and the subsequent recurrent “flu-like” symptoms. It has been speculated that both CFS and debilitating chronic fatigue (CF) that does not meet strict criteria for CFS may be the direct or indirect result of viral infections.

We therefore tested 548 chronically fatigued patients who underwent a comprehensive medical and psychiatric evaluation for antibodies to 13 viruses. Our objectives were to compare the seroprevalence and/or geometric mean titer (GMT) of antibodies to herpes simplex virus 1 and 2, rubella, adenovirus, human herpesvirus 6, Epstein-Barr virus, cytomegalovirus, and Cox-sackie B virus, types 1-6 in patients with CF to healthy control subjects. Other goals were to determine if greater rates of seropositivity or higher GMTs occurred among subsets of patients with CFS, fibromyalgia, psychiatric disorders, a self-reported illness onset with a viral syndrome, and a documented temperature > 37 degrees C on physical examination.

Differences in the seroprevalence or GMTs of antibodies to 13 viruses were not consistently found in those with CF compared with control subjects, or in any subsets of patients including those with CFS, an acute onset of illness, or a documented fever. These particular viral serologies were not useful in evaluating patients presenting with CF.

 

Source: Buchwald D, Ashley RL, Pearlman T, Kith P, Komaroff AL. Viral serologies in patients with chronic fatigue and chronic fatigue syndrome. J Med Virol. 1996 Sep;50(1):25-30. http://www.ncbi.nlm.nih.gov/pubmed/8890037

 

Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome

Abstract:

1. Chronic fatigue syndrome is characterized by muscle fatigue and pain at rest, symptoms which are usually exacerbated with exercise. Although various studies have shown minor, non-specific morphological and biochemical changes in muscle of patients with chronic fatigue syndrome, no consistent defect has been identified. Some have suggested that an enteroviral infection in muscle may cause the chronic muscle fatigue seen in patients with chronic fatigue syndrome, with acute infection directly and irreversibly impairing mitochondrial function, and persistent infection depressing muscle protein synthesis and metabolism.

2. To clarify the involvement of enterovirus infection in chronic fatigue syndrome, muscle biopsies from a group of patients with chronic fatigue syndrome were examined for the presence of enteroviral RNA by reverse transcriptase-polymerase chain reaction techniques in relation to functional studies of muscle mitochondria and the muscle RNA/DNA ratio.

3. Fifty-eight percent of patients reported an uncharacterized ‘viral infection’ before the onset of their illness, but none of the muscle samples from 34 patients contained detectable amounts of enteroviral RNA. Muscle tissue had a general reduction in the RNA/DNA ratio and mitochondrial enzyme activities with no specific abnormality in the activity of enzymes encoded partially on the mitochondrial genome (cytochrome-c oxidase) or nuclear genome (citrate synthase, succinate reductase).

4. These data provide no evidence of an enteroviral infection in muscle of patients with chronic fatigue syndrome, although this does not exclude a role of enterovirus in initiating the disease process. The general reduction in RNA/DNA ratio and mitochondrial enzyme activities is consistent with a general reduction in habitual activity.

 

Source: McArdle A, McArdle F, Jackson MJ, Page SF, Fahal I, Edwards RH. Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome. Clin Sci (Lond). 1996 Apr;90(4):295-300. http://www.ncbi.nlm.nih.gov/pubmed/8777836

 

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)

 

Use of anti HHV-6 transfer factor for the treatment of two patients with chronic fatigue syndrome (CFS). Two case reports

Abstract:

Specific Human Herpes virus-6 (HHV-6) transfer factor (TF) preparation, administered to two chronic fatigue syndrome patients, inhibited the HHV-6 infection. Prior to treatment, both patients exhibited an activated HHV-6 infection. TF treatment significantly improved the clinical manifestations of CFS in one patient who resumed normal duties within weeks, whereas no clinical improvement was observed in the second patient. It is concluded that HHV-6 specific TF may be of significant value in controlling HHV-6 infection and related illnesses.

 

Source: Ablashi DV, Levine PH, De Vinci C, Whitman JE Jr, Pizza G, Viza D. Use of anti HHV-6 transfer factor for the treatment of two patients with chronic fatigue syndrome (CFS). Two case reports. Biotherapy. 1996;9(1-3):81-6. http://www.ncbi.nlm.nih.gov/pubmed/8993763