Virus Studies

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Extended List of Studies (by year)

2015-2018

[HIGHLIGHT] Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model [PDF]
Blomberg J, Gottfries CG, Elfaitouri A, Rizwan M, Rosen A. Front Immunol. 2018
ME/CFS often starts after or during an infection. A logical explanation is that the infection initiates an autoreactive process, which affects several functions, including brain and energy metabolism. According to our model, patients with a genetic predisposition and dysbiosis experience a gradual development of B cell clones prone to autoreactivity. A decisive infectious trigger may then lead to immunization against autoantigens involved in aerobic energy production and/or hormone receptors and ion channel proteins, producing Post Exertional malaise and ME/CFS, affecting both muscle and brain.

[HIGHLIGHT] Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome. [PDF]
Loebel M, et al. Brain Behav Immun. 2016
We provide evidence that 29.5% of patients with CFS had elevated antibodies against one or more M acetylcholine and β adrenergic receptors which are potential biomarkers for response to B-cell depleting therapy. The association of autoantibodies with immune markers suggests that they activate B and T cells expressing β adrenergic and M acetylcholine receptors. Dysregulation of acetylcholine and adrenergic signalling could also explain various clinical symptoms of CFS.

Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). [PDF]
Rasa S, Nora-Krukle Z, Henning N, Eliassen E, Shikova E, Harrer T, Scheibenbogen C, Murovska M, Prusty BK, European Network on ME/CFS (EUROMENE). Journal of Translational Medicine. 2018
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease that causes central nervous system (CNS) and immune system disturbances, cell energy metabolisms and ion transport dysfunction, as well as cardiovascular problems, gastrointestinal dysfunction, cognitive impairment, myalgia, arthralgia, orthostatic intolerance, inflammation and innate immunity disturbances. The main clinical sign is persisting chronic fatigue, which is not relieved by rest and lasts for more than 6 months. A large group of patients remains wheelchair-dependent and many remain housebound or even bedbound.

The pathogenesis of ME/CFS is likely multi-factorial and various microbial and viral infections are considered to be the possible trigger factors of ME/CFS. The illness has been frequently accompanied with various viral infections and studies have been conducted on association of ME/CFS with Epstein–Barr virus (EBV) cytomegalovirus (CMV), human herpesvirus (HHV) 6, HHV-7, HHV-8, human parvovirus B19 (B19V), enteroviruses, lentivirus and bacteria as mycoplasma, Lyme disease causing borrelia, Q fever causing Coxiella burnetii  and other pathogens.

2010-2014

Is inherited human herpesvirus 6 the perpetrator behind some cases of chronic fatigue syndrome?
[Full Text] [PDF]
Lum E, Medveczky MM, Medveczky PG. Future Microbiol. 2014
The authors discuss the possible role of HHV 6 in CFS.

Increased risk of chronic fatigue syndrome following herpes zoster: a population-based study. [Full Text] [PDF]
Tsai SY, Yang TY, Chen HJ, Chen CS, Lin WM, Shen WC, Kuo CN, Kao CH. Eur J Clin Microbiol Infect Dis. 2014
Researchers in Taiwan identified more than 9,000 patients with herpes zoster (HZ) infection and 36,000 patients without herpes zoster infections. The incidence rate of CFS was higher in the HZ cohort than in the non-HZ cohort.

Detection of mycotoxins in patients with chronic fatigue syndrome. [PDF]
Brewer JH, Thrasher JD, Straus DC, Madison RA, Hooper D. Toxins (Basel). 2013
Urine specimens from 104 of 112 CFS patients (93%) were positive for at least one mycotoxin. Ochratoxin A was detected in 83% of samples and macrocyclic trichothecenes were detected in 44%.

[HIGHLIGHT] Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome. [PDF]
Montoya JG, et al. Journal of Medical Virology. 2013

Infection has been long suspected to be a trigger of CFS, as many patients recall the onset of their syndrome as an “influenza‐like” illness, and outbreaks of CFS have been reported in community and hospital settings [Briggs and Levine, 1994; Levine, 1994; Kerr et al., 2002; Hickie et al., 2006; Komaroff, 2006; Katz et al., 2009; Komaroff and Cho, 2011]. An aberrant immune response against periodic reactivation of or re‐infection with an infectious agent(s) has been proposed as a mechanism responsible for the perpetuation and fluctuation of the CFS symptoms [Tobi et al., 1982; Patnaik et al., 1995; Buchwald et al., 1996; Komaroff and Cho, 2011]. Thus, long‐term and pathogen‐directed interventions have been attempted in subsets of CFS patients who meet certain laboratory markers for a given organism with the hope to significantly ameliorate or end suffering [Kogelnik et al., 2006; Lerner et al., 2007].

Chronic fatigue syndrome 5 years after giardiasis: differential diagnoses, characteristics and natural course. [PDF]
Mørch K, Hanevik K, Rivenes AC, Bødtker JE, Næss H, Stubhaug B, Wensaas KA, Rortveit G, Eide GE, Hausken T, Langeland N. BMC Gastroenterol. 2013
A high prevalence of chronic fatigue has previously been reported following giardiasis after a large waterborne outbreak in Bergen, Norway in 2004. This study shows that Giardia duodenalis may induce CFS persisting as long as five years after the infection.

[HIGHLIGHT] Association of active human herpesvirus-6, -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome. [PDF]
Chapenko S, Krumina A, Logina I, Rasa S, Chistjakovs M, Sultanova A, Viksna L, Murovska M. Adv Virol. 2012
Active viral infection with HHV6, HHV7 and/or parvovirus B19 was found in 64.8% of patients and in 13.3% of practically healthy persons. Increase in peripheral blood leukocyte DNA HHV-6 load as well as in proinflammatory cytokines’ levels was detected in patients during active viral infection.

Immunophenotyping in post-giardiasis functional gastrointestinal disease and chronic fatigue syndrome. [PDF]
Hanevik K, Kristoffersen EK, Sørnes S, Mørch K, Næss H, Rivenes AC, Bødtker JE, Hausken T, Langeland N.
BMC Infect Dis. 2012
A Giardia outbreak was associated with development of post-infectious functional gastrointestinal disorders (PI-FGID) and chronic fatigue syndrome (PI-CFS). Five years later, researchers found significantly higher CD8 T-cell levels in PI-FGID, and significantly lower NK-cell levels in PI-CFS patients. Severity of abdominal and fatigue symptoms correlated negatively with NK-cell levels.

Antibody to Epstein-Barr virus deoxyuridine triphosphate nucleotidohydrolase and deoxyribonucleotide polymerase in a chronic fatigue syndrome subset. [PDF]
Lerner AM, Ariza ME, Williams M, Jason L, Beqaj S, Fitzgerald JT, Lemeshow S, Glaser R. PLoS One. 2012
There is prolonged elevated antibody level against the encoded proteins EBV dUTPase and EBV DNA polymerase in a subset of CFS patients.

Chronic fatigue syndrome after Giardia enteritis: clinical characteristics, disability and long-term sickness absence. [Full Text] [PDF]
Naess H, Nyland M, Hausken T, Follestad I, Nyland HI. BMC Gastroenterol. 2012
After a giardiasis enteritis outbreak, at least 5% of those affected developed clinical characteristics and functional impairment comparable to previously described post-infectious fatigue syndrome.

Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein-Barr virus IgG antibody titers.
Watt T, et al. J Med Virol. 2012

Acute enterovirus infection followed by myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and viral persistence. [Full Text] [PDF]
Chia J, Chia A, Voeller M, Lee T, Chang R. J Clin Pathol. 2010
Three representative patients with different manifestations of acute enterovirus infections progressed to have chronic symptoms of ME/CFS. Persistent viral infection was demonstrated in the antrum years later. Chronic enterovirus infection in an immunocompetent host may be an example of a stalemate between attenuated, intracellular viruses and an ineffective immune response.

Antibody to parvovirus B19 nonstructural protein is associated with chronic arthralgia in patients with chronic fatigue syndrome/myalgic encephalomyelitis. [Full Text] [PDF]
Kerr JR, Gough J, Richards SC, Main J, Enlander D, McCreary M, Komaroff AL, Chia JK. J Gen Virol. 2010
Eighty-three CFS patients (41.5 %) as compared with fourteen (7%) normal blood donors tested positive for anti-B19 NS1 IgG. Of these 83 patients, 61 complained of chronic joint pain, while 22 did not. Parvovirus B19 DNA was detected in serum of 11 CFS patients and none of the controls by Taqman real-time PCR. Positivity for anti-B19 NS1 IgG was associated with higher expression levels of the human CFS-associated genes NHLH1 and GABPA.

Viral infection leading to brain dysfunction: more prevalent than appreciated? [PDF]
van den Pol AN. Neuron. 2010

2005-2009

Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach. [Full Text]
Chia JK, Chia AY. J Clin Pathol. 2008
Enterovirus VP1, RNA and non-cytopathic viruses were detected in the stomach biopsy specimens of CFS patients with chronic abdominal complaints.

Chronic fatigue syndrome after human parvovirus B19 infection without persistent viremia. [Full Text]
Seishima M, Mizutani Y, Shibuya Y, Arakawa C. Dermatology. 2008
Some patients who get sick after a parvovirus B19 infection do not show antibodies.

Chronic fatigue syndrome and herpesvirus reactivation.
Kondo K. Nihon Rinsho. 2007
The amount of HHV-6 and HHV-7 reactivation has potential as a biomarker for CFS.

Chronic fatigue syndrome after Q fever. [Full Text]
Ledina D, Bradarić N, Milas I, Ivić I, Brncić N, Kuzmicić N. Med Sci Monit. 2007
Coxiella burnetii infection may be involved in the evolution of CFS.

Viral infections in chronic fatigue syndrome.
Sairenji T, Nagata K. Nihon Rinsho. 2007
The major hypothesis of the pathogenesis of CFS is that infectious agents such as viruses, may trigger and lead to chronic activation of the immune system with abnormal regulation of cytokine production. The authors summarize the recent progressive literature of virus, rickettsia, and mycoplasma implicated in the pathogenesis of CFS.

Activation of human herpesviruses 6 and 7 in patients with chronic fatigue syndrome. [Full Text]
Chapenko S, Krumina A, Kozireva S, Nora Z, Sultanova A, Viksna L, Murovska M. J Clin Virol. 2006
Reactivation of HHV6 and HHV7 in combination is frequent in CFS patients.

Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. [PDF]
Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A, Dubbo Infection Outcomes Study Group. BMJ. 2006.
We propose that alternative neurobiological mechanisms triggered during the severe, acute illness and sustained in the absence of ongoing peripheral inflammation underpin the persistent symptom domains of post-infective fatigue syndrome. Further longitudinal case-control studies in the post-infective model will allow testing of this hypothesis.

Is human herpesvirus-6 a trigger for chronic fatigue syndrome? [Full Text]
Komaroff AL. J Clin Virol. 2006
HHV6 is common in CFS and may serve to trigger and perpetuate the disease.

Pathogenesis of parvovirus B19 infection: host gene variability, and possible means and effects of virus persistence. [Full Text]
Kerr JR. J Vet Med B Infect Dis Vet Public Health. 2005
In a study of CFS patients, six genes were found to be differentially expressed with roles in the cytoskeleton (SKIP, MACF1, SPAG7, FLOT1), integrin signalling (FLOT1, RASSF5), HLA class III (c6orf48), and tumour suppression (RASSF5). These results have implications not only for B19 but also for other persistent viruses.

2000-2004

IgM serum antibodies to Epstein-Barr virus are uniquely present in a subset of patients with the chronic fatigue syndrome. [PDF]
Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT. In Vivo. 2004
Serum antibody to EBV VCA IgM may be a specific diagnostic test for a subset of CFS patients.

Epstein-Barr virus and human herpesvirus type 8 infections of the central nervous system.
Volpi A. Herpes. 2004

Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms. [Full Text]
Nicolson GL, Gan R, Haier J. APMIS. 2003
A large subset of CFS patients show evidence of bacterial and/or viral infection(s), and these infections may contribute to the severity of signs and symptoms found in these patients.

IgM serum antibodies to human cytomegalovirus nonstructural gene products p52 and CM2(UL44 and UL57) are uniquely present in a subset of patients with chronic fatigue syndrome.
Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT. In Vivo. 2002
The study suggests a relationship between CFS and human cytomegalovirus.

Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients. [PDF]
Ablashi DV, Eastman HB, Owen CB, Roman MM, Friedman J, Zabriskie JB, Peterson DL, Pearson GR, Whitman JE. J Clin Virol. 2000
In both MS and CFS patients, the authors found increased levels of HHV-6 antibody and HHV-6 DNA. A decrease in cellular immune responses was also detected in CFS patients.

PRE-2000

Multiple mycoplasmal infections detected in blood of patients with chronic fatigue syndrome and/or fibromyalgia syndrome. [PDF]
Nasralla M, Haier J, Nicolson GL. Eur J Clin Microbiol Infect Dis. 1999
More than 60% of patients with CFS were found to have mycoplasmal blood infections, such as Mycoplasma fermentans infection. More than half the patients had multiple infections.

Human herpesviruses in chronic fatigue syndrome. [PDF]
Wallace HL, et al. Clin Diagn Lab Immunol. 1999

Post-infection fatigue syndrome following Q fever.
Ayres JG, Flint N, Smith EG, Tunnicliffe WS, Fletcher TJ, Hammond K, Ward D, Marmion BP.QJM. 1998
The authors looked at a group of people who were infected with Q fever in 1989, finding CFS in 42.3% of cases and 26% of controls.

Chronic parvovirus B19 infection resulting in chronic fatigue syndrome: case history and review.
Jacobson SK, Daly JS, Thorne GM, McIntosh K. Clin Infect Dis. 1997
The authors report the case of a young woman with recurrent fever and a syndrome indistinguishable from chronic fatigue syndrome. After extensive investigation, they found persistent parvovirus B19 viremia, which was detectable by polymerase chain reaction (PCR) despite the presence of IgM and IgG antibodies to parvovirus B19. The patient’s fever resolved with the administration of intravenous immunoglobulin.

Severe stealth virus encephalopathy following chronic-fatigue-syndrome-like illness: clinical and histopathological features. [Full Text]
Martin WJ. Pathobiology. 1996
The clinical histories and brain biopsy findings of 3 patients with severe stealth virus encephalopathy are reviewed.

Chronic intestinal candidiasis as a possible etiological factor in the chronic fatigue syndrome.
Cater RE. Med Hypotheses. 1995
It is proposed that chronic intestinal candidiasis may be an agent which leads to immune depression in many CFS patients and therefore that it could be a causal factor in CFS.

Detection of enterovirus-specific RNA in serum: the relationship to chronic fatigue.
Clements GB, McGarry F, Nairn C, Galbraith DN. J Med Virol. 1995
Enteroviral specific sequences were detected in 36 of 88 serum samples from chronic fatigue patients and 3 of 126 healthy individuals.

Acute encephalopathy induced in cats with a stealth virus isolated from a patient with chronic fatigue syndrome. [Full Text] [PDF]
Martin WJ, Glass RT. Pathobiology. 1995
A simian cytomegalovirus-related stealth virus, isolated from a patient with the chronic fatigue syndrome, induced an acute neurological illness when inoculated into cats.

African green monkey origin of the atypical cytopathic ‘stealth virus’ isolated from a patient with chronic fatigue syndrome. [Full Text]
Martin WJ, Ahmed KN, Zeng LC, Olsen JC, Seward JG, Seehrai JS. Clin Diagn Virol. 1995
The findings implicate an African green monkey as the probable source of the “stealth” virus isolated from this CFS patient.

Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes.
Hilgers A, Frank J. Wien Med Wochenschr. 1994
A variety of immunological and hormonal abnormalities were found in a group of CFS patients.

The etiology and possible treatment of chronic fatigue syndrome/fibromyalgia.
Lund-Olesen LH, Lund-Olesen K. Med Hypotheses. 1994
It is suggested that chronic fatigue syndrome/fibromyalgia is caused by virus injury to the calcium channels leading to larger quantities than usual of calcium ions entering the striated muscle cells.

High titers of anti-Epstein-Barr virus DNA polymerase are found in patients with severe fatiguing illness.
Natelson BH, Ye N, Moul DE, Jenkins FJ, Oren DA, Tapp WN, Cheng YC. J Med Virol. 1994
Antibodies against EBV DNAP may be a useful marker in delineating a subset of patients with severe fatiguing illness.

[HIGHLIGHT] Enteroviruses and postviral fatigue syndrome.
Behan PO, Behan WM, Gow JW, Cavanagh H, Gillespie S. Ciba Found Symp. 1993
An increase in the number and size of muscle mitochondria was found in 70% of postviral fatigue cases cases, suggesting an abnormality in metabolic function. Evidence of hypothalamic dysfunction was present, particularly involving 5-hydroxytryptamine metabolism.

Persistence of enterovirus RNA in muscle biopsy samples suggests that some cases of chronic fatigue syndrome result from a previous, inflammatory viral myopathy.
*Bowles NE, Bayston TA, Zhang HY, Doyle D, Lane RJ, Cunningham L, Archard LC. J Med. 1993
CFS may be a sequela of a previous inflammatory viral myopathy.

Amplification and identification of enteroviral sequences in the postviral fatigue syndrome.
Gow JW, Behan WM. Br Med Bull. 1991
A highly significant number of muscle biopsies from CFS patients were positive for enteroviral sequences.

Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with post viral fatigue syndrome. [PDF]
Gow JW, Behan WM, Clements GB, Woodall C, Riding M, Behan PO. BMJ. 1991
Persistent enteroviral infection of muscle may occur in some patients with post viral fatigue syndrome.

HHV-6 reactivation in chronic fatigue syndrome.
Josephs SF, Henry B, Balachandran N, Strayer D, Peterson D, Komaroff AL, Ablashi DV Lancet. 1991
HHV-6 is reported to be reactivated in CFS.

A chronic “postinfectious” fatigue syndrome associated with benign lymphoproliferation, B-cell proliferation, and active replication of human herpesvirus-6.
Buchwald D, Freedman AS, Ablashi DV, Sullivan JL, Caligiuri M, Weinberg DS, Hall CG, Ashley RL, Saxinger C, Balachandran N, et al. J Clin Immunol. 1990
A patient with ME and HHV6 is profiled.

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. [Full Text] [PDF]
Cunningham L, Bowles NE, Lane RJ, Dubowitz V, Archard LC. J Gen Virol. 1990
This study suggests that enterovirus persistence in muscle is due to a defect in control of viral RNA synthesis.

Human B-lymphotropic virus (human herpesvirus-6). [Full Text]
Ablashi DV, Josephs SF, Buchbinder A, Hellman K, Nakamura S, Llana T, Lusso P, Kaplan M, Dahlberg J, Memon S, et al. J Virol Methods. 1988
Human B-lymphotropic virus (HBLV), also known as human herpesvirus-6 (HHV-6), is elevated in AIDS patients and patients with chronic fatigue syndrome.

Postviral fatigue syndrome: persistence of enterovirus RNA in muscle and elevated creatine kinase.
[Full Text] [PDF]
Archard LC, Bowles NE, Behan PO, Bell EJ, Doyle D. J R Soc Med. 1988