Virus and cfs

Detection of enterovirus-specific RNA in serum: the relationship to chronic fatigue. Comparison of coxsackie B neutralisation and enteroviral PCR in chronic fatigue patients. Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome. Enterovirus related metabolic myopathy: a postviral fatigue syndrome. J Neurol Neurosurg Psychiatry.

Persistence of enterovirus RNA in muscle biopsy samples suggests that some cases of chronic fatigue syndrome result from a previous, inflammatory viral myopathy. J Med. Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA.

Detection of enterovirus in human skeletal muscle from patients with chronic inflammatory muscle disease or fibromyalgia and healthy subjects. Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach. Phylogenetic analysis of short enteroviral sequences from patients with chronic fatigue syndrome. Evidence for enteroviral persistence in humans.

Ribavirin and interferon-a for the treatment of patients with chronic fatigue syndrome associated with persistent coxsackievirus b infection: a preliminary observation. J Appl Res. Enteroviruses and the chronic fatigue syndrome. No findings of enteroviruses in Swedish patients with chronic fatigue syndrome.

Scand J Infect Dis. Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome.

Clin Sci Lond ; 90 — Studies on enterovirus in patients with chronic fatigue syndrome. Parvovirus-like particles in human sera. Parvovirus infections and hypoplastic crisis in sickle-cell anaemia. Kerr JR. Pathogenesis of human parvovirus B19 in rheumatic disease. Ann Rheum Dis. The role of parvovirus B19 in the pathogenesis of autoimmunity and autoimmune disease. Neurological aspects of human parvovirus B19 infection: a systematic review. Rev Med Virol.

Cytokines in parvovirus B19 infection as an aid to understanding chronic fatigue syndrome. Curr Pain Headache Rep. Absence of parvovirus B19 infection in chronic fatigue syndrome. Arthritis Rheum. Preexisting psychological stress predicts acute and chronic fatigue and arthritis following symptomatic parvovirus B19 infection. No apparent difference in the prevalence of parvovirus B19 infection between chronic fatigue syndrome patients and healthy controls in Japan.

PLoS Pathog. Recombinant origin of the retrovirus XMRV. Ribonuclease L proteolysis in peripheral blood mononuclear cells of chronic fatigue syndrome patients. J Biol Chem. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Alberts B. Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors. Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome. Failure to detect Xenotropic murine leukaemia virus-related virus in Chinese patients with chronic fatigue syndrome.

Virol J. Absence of evidence of Xenotropic murine leukemia virus-related virus infection in persons with chronic fatigue syndrome and healthy controls in the United States. Absence of Xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome. No association of Xenotropic murine leukemia virus-related virus with prostate cancer or chronic fatigue syndrome in Japan.

Serologic and PCR testing of persons with chronic fatigue syndrome in the United States shows no association with xenotropic or polytropic murine leukemia virus-related viruses.

Prevalence of Xenotropic murine leukaemia virus-related virus in patients with chronic fatigue syndrome in the Netherlands: retrospective analysis of samples from an established cohort. Front Public Health. Smith RA. Phylogenetic analysis of murine leukemia virus sequences from longitudinally sampled chronic fatigue syndrome patients suggests PCR contamination rather than viral evolution.

J Virol. Absence of XMRV retrovirus and other murine leukemia virus-related viruses in patients with chronic fatigue syndrome. No association found between the detection of either Xenotropic murine leukemia virus-related virus or polytropic murine leukemia virus and chronic fatigue syndrome in a blinded, multi-site, prospective study by the establishment and use of the SolveCFS BioBank.

BMC Res Notes. Multiple sources of contamination in samples from patients reported to have XMRV infection. Xenotropic murine leukemia virus-related virus XMRV and the safety of the blood supply. Clin Microbiol Rev. Search for retrovirus in the chronic fatigue syndrome. Assessment of a retrovirus sequence and other possible risk factors for the chronic fatigue syndrome in adults.

Changing epidemiology of Ross River virus disease in South Australia. Med J Aust. Lidbury BA, Mahalingam S. Specific ablation of antiviral gene expression in macrophages by antibody-dependent enhancement of Ross River virus infection.

Mahalingam S, Lidbury BA. Suppression of lipopolysaccharide-induced antiviral transcription factor STAT-1 and NF-kappa B complexes by antibody-dependent enhancement of macrophage infection by Ross River virus. Production of pro-inflammatory cytokines correlates with the symptoms of acute sickness behaviour in humans.

Psychol Med. Peripheral blood gene expression in postinfective fatigue syndrome following from three different triggering infections. Neurocognitive disturbances associated with acute infectious mononucleosis, Ross River fever and Q fever: a preliminary investigation of inflammatory and genetic correlates. Nijs J, Fremont M.

Expert Opin Ther Targets. A formal analysis of cytokine networks in chronic fatigue syndrome. Glassford JA. Sairenji T, Nagata K. Viral infections in chronic fatigue syndrome. Nihon Rinsho. Assessment of immune mediator expression levels in biological fluids and cells: a critical appraisal. Crit Rev Oncog. J Affect Disord. A chronic fatigue syndrome model demonstrates mechanical allodynia and muscular hyperalgesia via spinal microglial activation.

Cross-reactivity with myelin basic protein and human herpesvirus-6 in multiple sclerosis. Ann Neurol. J Immunol. Coxsackievirus counters the host innate immune response by blocking type III interferon expression. Innate immunity and immune evasion by enterovirus Front Microbiol. Human herpesvirus 6B downregulates expression of activating ligands during lytic infection to escape elimination by natural killer cells.

J Cancer. Lusso P. HHV-6 and the immune system: mechanisms of immunomodulation and viral escape. Cytokine homologs of human gammaherpesviruses. J Interferon Cytokine Res. Human herpesviridae methods of natural killer cell evasion.

Coxsackievirus B3 inhibits antigen presentation in vivo, exerting a profound and selective effect on the MHC class I pathway. Type B coxsackieviruses and their interactions with the innate and adaptive immune systems. Future Microbiol. Circulating tumour necrosis factor-alpha and interferon-gamma are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue.

Infection and vaccination in chronic fatigue syndrome: myth or reality? Acute parvovirus B19 infection mimicking chronic fatigue syndrome. Intern Med. Chehadeh W, Alkhabbaz M. Differential TLR7-mediated expression of proinflammatory and antiviral cytokines in response to laboratory and clinical enterovirus strains. Association study of inflammatory cytokine and chemokine expression in hand foot and mouth disease. Herpesvirus evasion of natural killer cells. Association of mitochondrial dysfunction and fatigue: a review of the literature.

BBA Clin. Chronic fatigue syndrome and mitochondrial dysfunction. Int J Clin Exp Med. The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: peripheral and central mechanisms as therapeutic targets?

Metabolic features of chronic fatigue syndrome revisited. Metabolic features of chronic fatigue syndrome. Mitochondrial distribution and function in herpes simplex virus-infected cells.

The antiapoptotic herpes simplex virus glycoprotein J localizes to multiple cellular organelles and induces reactive oxygen species formation. Herpes simplex virus eliminates host mitochondrial DNA. EMBO Rep. Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr virus. BMC Infect Dis. Epstein—Barr virus latent membrane protein-2A alters mitochondrial dynamics promoting cellular migration mediated by Notch signaling pathway.

Epstein—Barr virus immediate-early protein Zta co-opts mitochondrial single-stranded DNA binding protein to promote viral and inhibit mitochondrial DNA replication. The U95 protein of human herpesvirus 6B interacts with human GRIM silencing of U95 expression reduces viral load and abrogates loss of mitochondrial membrane potential.

Imbalanced oxidative stress causes chlamydial persistence during non-productive human herpes virus co-infection. Human herpesvirus 6A induces apoptosis of HSB-2 cells via a mitochondrion-related caspase pathway. J Biomed Res. Presence of cytomegalovirus DNA in leucocytes is associated with increased oxidative stress and subclinical atherosclerosis in healthy adults.

Modulation of mitochondrial antiviral signaling by human herpesvirus 8 interferon regulatory factor 1. Role of mitochondria in parvovirus pathology. Porcine parvovirus infection activates mitochondria-mediated apoptotic signaling pathway by inducing ROS accumulation. Scientists have detected the DNA of a retrovirus in the blood of patients with chronic fatigue syndrome.

The discovery raises the possibility that the virus may be a contributing factor in chronic fatigue syndrome. Chronic fatigue syndrome, or CFS, is a debilitating disease that affects millions of people in the United States. It's characterized by profound fatigue that doesn't improve with bed rest and can be exacerbated or re-kindled by physical or mental activity.

A number of other symptoms are also associated with CFS, including cognitive deficits, impaired sleep, myalgia, arthralgia, headache, gastrointestinal symptoms and tender lymph nodes. No specific cause for CFS has yet been identified. Share on: Facebook Twitter. Show references Kellerman RD, et al. In: Conn's Current Therapy Elsevier; Accessed Feb 4, Gluckman SJ.

Accessed Feb. Ferri FF. Chronic fatigue syndrome. In: Ferri's Clinical Advisor Centers for Disease Control and Prevention. Seven patients had a significant improvement of fatigue and other flu-like symptoms while on Ribavirin, but relapsed one to two weeks after discontinuation.

All seven patients had a fourfold or greater reduction of neutralising antibody while on treatment, but the values increased post-treatment when the patients relapsed. Enteroviral RNA became negative two to four weeks after the start of treatment. Fatigue did not improve during treatment probably because of the side effects of the interferon.

However, relapse occurred in four patients about four to five months post-treatment; the antibody titre increased to pretreatment values in all four patients and the enteroviral RNA became positive at least once in all of the patients who relapsed.

The patient returned to full time work two months after the treatment was completed. Enteroviral RNA remained negative until she had a transient symptomatic and virological relapse after vigorous exercise.

Remission lasted about 14 months before the symptoms returned to the pretreatment baseline. The patient responded to an additional course of interferon treatment. No commercial funding is currently available for a placebo controlled study.

The arrow indicates vigorous exercise after treatment. The graphs show clearance of circulating viral RNA after antiviral treatment, and an association between vigorous exercise, reappearance of circulating viral RNA, and decreased energy. Three patients had no symptomatic improvement while on or after one week of drug treatment, at a dose of mg three times a day, and there was no change of antibody titre after the treatment.

One patient had a moderate symptomatic improvement while taking Pleconaril mg three times a day for one month, along with a fourfold decrease of antibody titres for CVB4 and echoviruses 7 and However, she relapsed about one month later, and did not respond to a further month of treatment. As of March , the oral form of Pleconaril is no longer available for investigational use. Taken together, these data suggest that enterovirus can initiate and perpetuate the immunological response often seen in patients with CFS.

Smouldering viral infection of various cells of the body with continuous expression of double stranded RNA and viral antigens could result in a chronic inflammatory state in the local tissues and account for the diverse symptoms reported by these patients.

The mechanism of viral persistence reconciles the two seemingly opposing observations of the past two decades: absence of live virion in chronically infected patients and animals and the finding of enteroviral RNA in the blood or other tissues. In contrast, patients with CFS and the presence of viral RNA in peripheral blood leucocytes or in tissues, but without true viraemia, have debilitating symptoms; the severity of the symptoms correlated with the frequency of finding enteroviral RNA in the peripheral blood leucocytes J Chia and A Chia.

In most of the patients with CFS, the cyclic nature of low grade febrile illness and severe exacerbation after physical activity would be consistent with a cyclical pattern in the viral replicative activity. It is probable that viral RNA found inside cells, in a stable double stranded form, can dissociate and replicate using viral RNA replicase; some of the positive strands, although restricted in replication, 51 are translated to viral proteins during active metabolic states for instance, exercise , which subsequently perpetuates the immunological response, including but not limited to synthesis of specific neutralising antibody.

Among other immunostimulatory effects, double stranded RNA is a potent inducer of interferon synthesis, which activates intracellular RNase, with resultant degradation of excessive single stranded RNA. The finding of a higher level of RNase L activity in the mononuclear cells of patients with CFS is consistent with this paradigm. A severe flu-like illness occurs in most cases of chronic fatigue syndrome CFS , suggesting that an infection triggers and possibly perpetuates this syndrome.

Common viral infections and unusual causes of CFS could be diagnosed based on the details of the initial flu-like illness, if present, epidemiological history, and early virological testing. Viral persistence through the formation of stable double stranded RNA reconciles the two opposing observations of the past two decades: 1 the absence of live virion in chronically infected patients and animals and 2 the presence of enteroviral RNA in the blood or other tissues.

Smouldering viral infection of various cells with continuous expression of double stranded RNA and viral antigens could result in a chronic inflammatory state in the local tissues, accounting for the diverse symptoms. Self replicating double stranded RNA molecules replicons have been well studied and are currently used as vectors for DNA vaccines and drug susceptibility assays.

The paradox remains, however, that despite an ongoing immune response, these viral RNA infected cells are not eradicated. It is possible that viruses hide in long living, immunologically privileged cells, including but not limited to, macrophages, muscles, myocardial cells, and neurones, 28— 37 although these cells are unable to produce much live viruses, perhaps, in part, because of the pressure from local interferon and high concentrations of neutralising antibody—a form of cryptic infection.

Viral antigen has been identified in tissues by virus specific monoclonal antibodies but positive staining did not allow the differentiation between membrane bound viral proteins and sequestered virions.

Thus, renewed interest is needed to study further the role of enterovirus as the causative agent of CFS. Many aspects of this research need to be addressed but there are three urgent priorities. In the future, a well designed, randomised, controlled trial of antiviral treatment will ultimately provide crucial information on the pathogenic role of enterovirus in patients with CFS and other chronic diseases.

National Center for Biotechnology Information , U. Journal List J Clin Pathol v. J Clin Pathol. J K S Chia. Author information Article notes Copyright and License information Disclaimer. Accepted Mar This article has been cited by other articles in PMC. Abstract Two and a half decades after coining of the term chronic fatigue syndrome CFS , the diagnosis of this illness is still symptom based and the aetiology remains elusive. Keywords: enterovirus, chronic fatigue syndrome, double stranded RNA, viral persistence.

Open in a separate window. Figure 1. Acknowledgments The laboratory work was supported by the Chu-Lee Tu memorial research fund. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med ; —9. Identification of ambiguities in the chronic fatigue syndrome research case definition and recommendations for resolution.

Post-viral fatigue syndrome. Epstein-Barr virus and human disease Clifton, New Jersey: Humana Press, — Levy JA. Viral studies of chronic fatigue syndrome: introduction.

Clin Infect Dis ; 18 suppl 1 :S— Chronic Chlamydia pneumoniae infection, a treatable cause of chronic fatigue syndrome. Clin Infect Dis ; 29 —3.