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

 

No findings of enteroviruses in Swedish patients with chronic fatigue syndrome

Abstract:

Enteroviruses have been proposed to cause an immune complex disease in the chronic fatigue syndrome. Altogether 34 patients with the chronic fatigue syndrome, according to criteria of the Centers for Disease Control, USA, were studied evenly over the seasons for the possible presence of a chronic enterovirus infection.

In 11 patients, 1-5 faecal samples were collected at about 6 month intervals for virus isolation before and after acid treatment, followed by ultracetrifugation at pH 3 to dissolve possible enterovirus-antibody complexes. Another 14 fecal samples were subjected to routine virus isolation alone.

Seven pairs of serum-cerebrospinal fluid samples were analysed for cross-reactive IgG antibody activity to enteroviruses. In 29 patients a muscle biopsy was collected for enterovirus polymerase chain reaction (PCR).

We were unable to identify enteroviruses in any of these samples by any of these techniques. Our study does not confirm evidence for persistent enterovirus infection in the chronic fatigue syndrome.

 

Source: Lindh G, Samuelson A, Hedlund KO, Evengård B, Lindquist L, Ehrnst A. No findings of enteroviruses in Swedish patients with chronic fatigue syndrome. Scand J Infect Dis. 1996;28(3):305-7. http://www.ncbi.nlm.nih.gov/pubmed/8863367

 

Genetic instability and fragmentation of a stealth viral genome

Abstract:

Partial sequencing was performed on cloned DNA obtained from cultures of a stealth virus isolated from a patient with the chronic fatigue syndrome. The results extend earlier findings showing regions of homology to cytomegalovirus (CMV). Although the virus is much more closely related to simian CMV than to human CMV, many of the cloned viral segments could be aligned with the human CMV genome.

The aggregate size of the aligned segments exceeds 100 kilobase pairs (kbp). Undigested viral DNA has a mobility in agarose gel electrophoresis corresponding to approximately 20 kbp. The virus, therefore, apparently exists in multiple fragments. Considerable sequence variation exists between individual clones which overlap to similar regions of the human CMV genome.

The fragmented genome and sequence microheterogeneity suggest that both the processivity and the fidelity of replication of the viral genome are defective. An unstable viral genome may provide a potential mechanism of recovery from stealth viral illness.

 

Source: Martin WJ. Genetic instability and fragmentation of a stealth viral genome. Pathobiology. 1996;64(1):9-17. http://www.ncbi.nlm.nih.gov/pubmed/8856790

 

Severe stealth virus encephalopathy following chronic-fatigue-syndrome-like illness: clinical and histopathological features

Abstract:

The clinical histories and brain biopsy findings of 3 patients with severe stealth virus encephalopathy are reviewed. The patients initially developed symptoms consistent with a chronic fatigue syndrome. One patient has remained in a vegetative state for several years, while the other 2 patients have shown significant, although incomplete, recovery.

Histological and electron-microscopic studies revealed vacuolated cells with distorted nuclei and various cytoplasmic inclusions suggestive of incomplete viral expression. There was no significant inflammatory response. Viral cultures provided further evidence of stealth viral infections occurring in these patients.

 

Source: Martin WJ. Severe stealth virus encephalopathy following chronic-fatigue-syndrome-like illness: clinical and histopathological features. Pathobiology. 1996;64(1):1-8. http://www.ncbi.nlm.nih.gov/pubmed/8856789