Tag: enteroviruses

Enteroviruses in chronic fatigue syndrome: “now you see them, now you don’t”

Comment on: Enterovirus related metabolic myopathy: a postviral fatigue syndrome. [J Neurol Neurosurg Psychiatry. 2003]

 

In the paper by Lane et al(see pp 1382– 1386)1 an association was found between abnormal exercise lactate response and enterovirus sequences in the muscle of some patients with chronic fatigue syndrome (CFS). The paper rekindles the old saga of enteroviruses, muscle inflammation, and fatigue.

You can read the rest of this comment here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1757390/pdf/v074p01361.pdf

 

Source: Dalakas MC. Enteroviruses in chronic fatigue syndrome: “now you see them, now you don’t”. J Neurol Neurosurg Psychiatry. 2003 Oct;74(10):1361-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1757390/  (Full article)

 

Detection of enterovirus in human skeletal muscle from patients with chronic inflammatory muscle disease or fibromyalgia and healthy subjects

Abstract:

Enterovirus RNA has been found previously in specimens of muscle biopsy from patients with idiopathic dilated cardiomyopathy, chronic inflammatory muscle diseases, and fibromyalgia or chronic fatigue syndrome (fibromyalgia/chronic fatigue syndrome). These results suggest that skeletal muscle may host enteroviral persistent infection.

To test this hypothesis, we investigated by reverse transcription-polymerase chain reaction (RT-PCR) assay the presence of enterovirus in skeletal muscle of patients with chronic inflammatory muscle diseases or fibromyalgia/chronic fatigue syndrome, and also of healthy subjects.

Three of 15 (20%) patients with chronic inflammatory muscle diseases, 4 of 30 (13%) patients with fibromyalgia/chronic fatigue syndrome, and none of 29 healthy subjects was found positive. The presence of VP-1 enteroviral capsid protein was assessed by an immunostaining technique using the 5-D8/1 monoclonal antibody; no biopsy muscle from any patient or healthy subject was found positive.

The presence of viral RNA in some muscle biopsies from patients exhibiting muscle disease, together with the absence of VP-1 protein, is in favor of a persistent infection involving defective viral replication.

Copyright 2003 Wiley-Liss, Inc.

 

Source: Douche-Aourik F, Berlier W, Féasson L, Bourlet T, Harrath R, Omar S, Grattard F, Denis C, Pozzetto B. Detection of enterovirus in human skeletal muscle from patients with chronic inflammatory muscle disease or fibromyalgia and healthy subjects. J Med Virol. 2003 Dec;71(4):540-7. http://www.ncbi.nlm.nih.gov/pubmed/14556267

 

Enterovirus infections in new disguise

Abstract:

Enteroviruses (Coxsackie A and B, echovirus, poliovirus) belong to a group of small RNA-viruses, picomavirus, which are widespread in nature. Enteroviruses cause a number of well known diseases and symptoms in humans, from subclinical infections and the common cold to poliomyelitis with paralysis. The development of polio vaccines is the greatest accomplishment within the field of enterovirus research and the background work was awarded the Nobel prize in 1954. New knowledge implies that enteroviruses play a more important part in the morbidity panorama than was previously thought. Chronic (persistent) enteroviruses were formerly unknown.

Serologic and molecular biology techniques have now demonstrated that enteroviral genomes, in certain situations, persist after the primary infection (which is often silent). Persistent enteroviral infection or recurrent infections and/or virus-stimulated autoimmunity might contribute to the development of diseases with hitherto unexplained pathogenesis, such as post polio syndrome, dilated cardiomyopathy, juvenile (type 1) diabetes and possibly some cases of chronic fatigue syndrome.

 

Source: Fohlman J, Friman G, Tuvemo T. Enterovirus infections in new disguise. Lakartidningen. 1997 Jul 9;94(28-29):2555-60. [Article in Swedish] http://www.ncbi.nlm.nih.gov/pubmed/9254324

 

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

 

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

 

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

 

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

 

Comparison of coxsackie B neutralisation and enteroviral PCR in chronic fatigue patients

Abstract:

Coxsackie B enteroviruses have been implicated repeatedly as agents associated with chronic fatigue syndrome (CFS). The objective of this study was to compare the serological evidence for the presence of Coxsackie B virus neutralising antibody, with the polymerase chain reaction (PCR) detecting a portion of the 5′ nontranslated region (NTR) of the enterovirus genome.

Serum samples from 100 chronic fatigue patients and from 100 healthy comparison patients were used in this study. In the CFS study group, 42% patients were positive for enteroviral sequences by PCR, compared to only 9% of the comparison group. Using the neutralisation assay, 34% of study patients were positive, compared to 41% of comparison patients.

In the study group, 66/100 patient results correlated, i.e., they were either positive/positive or negative/negative for both tests. Of those that did not correlate, the majority were PCR-positive/Coxsackie B antibody-negative (21/34).

In the comparison group, 58/100 patient results correlated. Of those that did not, the majority were PCR-negative/Coxsackie B antibody-positive (37/42).

The Coxsackie B antibody neutralisation assay was not able to differentiate the CFS study group from the healthy comparison group, and thus the clinical relevance of this assay may be questioned. The PCR assay did differentiate the two groups with significantly more CFS patients having evidence of enterovirus than the comparison group.

Source: Nairn C, Galbraith DN, Clements GB. Comparison of coxsackie B neutralisation and enteroviral PCR in chronic fatigue patients. J Med Virol. 1995 Aug;46(4):310-3. http://www.ncbi.nlm.nih.gov/pubmed/7595406

 

Enteroviruses and the chronic fatigue syndrome

Abstract:

The possible role of enteroviral persistence in the etiology of the chronic fatigue syndrome (CFS) was investigated by serological testing, VP-1 antigen testing, and polymerase chain reaction (PCR) analysis of stool specimens as well as by viral cultures of stool–both direct and after acid treatment. No differences between 76 patients with disabling unexplained fatigue and 76 matched controls were found by serological or antigen testing.

Furthermore, no enteroviruses were isolated from any stool culture. Enterovirus was detected by PCR in one stool specimen from a patient with CFS but was not detectable in a second sample obtained from the same patient 3 months later. All stool specimens from controls were PCR-negative. These results argue against the hypothesis that enteroviruses persist in patients with CFS and that their persistence plays a role in the pathogenesis of this syndrome.

 

Source: Swanink CM, Melchers WJ, van der Meer JW, Vercoulen JH, Bleijenberg G, Fennis JF, Galama JM. Enteroviruses and the chronic fatigue syndrome. Clin Infect Dis. 1994 Nov;19(5):860-4. http://www.ncbi.nlm.nih.gov/pubmed/7893870

 

Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response?

Abstract:

As a test of the hypothesis that elevated titers of viral antibodies in patients with chronic fatigue syndrome (CFS) are due to a nonspecific polyclonal immune response, antibodies to Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and 14 enteroviruses in 20 patients with CFS and 20 age- and gender-matched controls were simultaneously measured.

Similarly, titers of IgG to herpes simplex virus (HSV) types 1 and 2 were measured in 18 of these cases and in the respective controls. IgG to EBV viral capsid antigen (VCA) was present at titers > or = 1:320 in 55% of cases vs. 15% of controls (P = .02).

The geometric mean titers of early antigen antibody to EBV, HHV-6 IgG, and HSV-1 and HSV-2 IgG were not significantly different among cases and controls. Of the 14 enteroviral antibodies tested for, only those to coxsackieviruses B1 and B4 were present at significant titers (> or = 1:8) in cases vs. controls (P = .02 and P = .001, respectively).

Of the cases, 19 (95%) had either an EBV VCA IgG titer > or = 1:320 or a coxsackievirus B1 or B4 antibody titer > or = 1:8, a percentage significantly higher than that of controls (40%; P = .0004). Titers of EBV VCA IgG and coxsackievirus B1 and B4 antibodies were simultaneously elevated in only 20% of cases.

There was no correlation between elevated titers of EBV VCA IgG and IgG to HHV-6, HSV-1, and HSV-2 or antibody to coxsackieviruses B1 and B4 in the cases. The prevalence of reported allergies to medications or other substances was identical in both groups (60%). These findings suggest that in the majority of cases of CFS, elevation of viral antibody titers is not due to a nonspecific polyclonal immune response.

Comment in: Viral antibodies in chronic fatigue syndrome. [Clin Infect Dis. 1995]

 

Source: Manian FA. Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response? Clin Infect Dis. 1994 Sep;19(3):448-53. http://www.ncbi.nlm.nih.gov/pubmed/7811864