Category: Viruses

Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating disease of unknown etiology that is estimated to affect 17 million people worldwide. Studying peripheral blood mononuclear cells (PBMCs) from CFS patients, we identified DNA from a human gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), in 68 of 101 patients (67%) as compared to 8 of 218 (3.7%) healthy controls. Cell culture experiments revealed that patient-derived XMRV is infectious and that both cell-associated and cell-free transmission of the virus are possible. Secondary viral infections were established in uninfected primary lymphocytes and indicator cell lines after their exposure to activated PBMCs, B cells, T cells, or plasma derived from CFS patients. These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS.

Comment in:

Erratum in: Partial retraction. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. [Science. 2011]

Retraction in: Retraction. [Science. 2011]

 

Source: Lombardi VC, Ruscetti FW, Das Gupta J, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M, Silverman RH, Mikovits JA. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science. 2009 Oct 23;326(5952):585-9. doi: 10.1126/science.1179052. Epub 2009 Oct 8. http://science.sciencemag.org/content/326/5952/585.long (Full article)

 

Virology. A new virus for old diseases?

There is little consensus in the medical community on whether chronic fatigue syndrome is a distinct disease. As its name implies, the condition is characterized by debilitating fatigue persisting for many years, and it affects as much as 1% of the world’s population. Although chronic inflammation is often found in these patients, no infectious or toxic agent has been clearly implicated in this disease, which is diagnosed largely by excluding other conditions that cause similar symptoms (1). In this week’s Science Express, Lombardi et al. (2) describe the detection of xenotropic murine leukemia virus–related virus (XMRV) in about two-thirds of patients diagnosed with chronic fatigue syndrome. Both laboratory and epidemiological studies are now needed to determine whether this virus has a causative role, not only in this disease, but perhaps in others as well.

Chronic fatigue syndrome is not the first human disease to which XMRV has been linked. The virus first was described about 3 years ago in a few prostate cancer patients (3), and recently detected in nearly a quarter of all prostate cancer biopsies (4). It has been isolated from both prostate cancer and chronic fatigue syndrome patients, and is similar to a group of endogenous murine leukemia viruses (MLVs) found in the genomes of inbred and related wild mice. Although a half century of studies on MLVs and other gammaretroviruses have led to important discoveries on which much of our current understanding of cancer rests, there has been no clear evidence demonstrating human infection with gammaretroviruses, or associating these agents with any human disease.

You can read the rest of this article here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818280/

Comment on: Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. [Science. 2009]

 

Source: Coffin JM, Stoye JP. Virology. A new virus for old diseases? Science. 2009 Oct 23;326(5952):530-1. doi: 10.1126/science.1181349. Epub 2009 Oct 8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818280/ (Full article)

 

Sensitive, qualitative detection of human herpesvirus-6 and simultaneous differentiation of variants A and B

Abstract:

BACKGROUND: The current limitations of laboratory testing for the detection of human herpesvirus virus 6 (HHV-6) in clinical specimens with low HHV-6 viral loads make this area a priority for further research and development.

OBJECTIVES: To develop and validate a sensitive qualitative assay for simultaneous HHV-6 detection and variant differentiation.

METHODS: We developed a diagnostic procedure, which combines a magnetic bead-based nucleic acid extraction, PCR amplification, and colorimetric microtiter plate identification (MAG-PCR-EIA), for the sensitive detection of HHV-6 and the simultaneous differentiation of HHV-6A and HHV-6B.

RESULTS: Analytic sensitivities of the MAG-PCR-EIA assay were 10 copies per reaction for both HHV-6A and HHV-6B variants, which is equivalent to 20 copies/ml when 1ml of clinical specimen was processed. A proficiency panel containing 11 blinded specimens covering HHV-6A viral loads from 0 to 100,000 copies was tested, and the MAG-PCR-EIA was able to detect the lowest concentration at one copy in 200microl. A panel of 27 urine specimens, which were collected from patients with and without chronic fatigue syndrome, was tested by the MAG-PCR-EIA. HHV-6 was detected in two (HHV-6A) patients who have chromosomally integrated HHV-6A and in one (HHV-6B) patient who was a healthy control and diagnosed as cervical cancer later on. The HHV-6 results did not correlate with results previously determined by HHV-6 antigenemia in urine.

CONCLUSION: With large specimen volumes processed and an additional signal amplification incorporated, the MAG-PCR-EIA provides a sensitive and qualitative system for HHV-6 detection and simultaneous variant differentiation. Clinical relevance of the assay awaits further investigation.

 

Source: Li H, Meng S, Levine SM, Stratton CW, Tang YW. Sensitive, qualitative detection of human herpesvirus-6 and simultaneous differentiation of variants A and B. J Clin Virol. 2009 Sep;46(1):20-3. doi: 10.1016/j.jcv.2009.05.016. Epub 2009 Jun 21. https://www.ncbi.nlm.nih.gov/pubmed/19540801

 

Does varicella-zoster virus infection of the peripheral ganglia cause Chronic Fatigue Syndrome?

Abstract:

This article posits that infection of the peripheral ganglia causes at least some cases of Chronic Fatigue Syndrome (CFS), with a neurotropic herpesvirus, particularly varicella-zoster virus (VZV), as the most likely cause of the infection. Virtually all CFS symptoms could be produced by an infection of the peripheral ganglia, with infection of the autonomic ganglia causing fatigue, postural hypotension, and sleep disturbances, and infection of the sensory ganglia causing sensory symptoms such as chronic pain. Furthermore, infections of the peripheral ganglia are known to cause long-term nerve dysfunction, which would help explain the chronic course of CFS.

Herpesviruses have long been suspected as the cause of CFS; this theory has recently been supported by studies showing that administering antiherpes agents causes substantial improvement in some CFS patients. VZV is known to frequently reactivate in the peripheral ganglia of previously healthy adults and cause sudden, debilitating illness, making it a likely candidate as a cause of CFS. Moreover, many of the symptoms of CFS overlap with those of herpes zoster (shingles), with the exception that painful rash is not one of the symptoms of CFS.

A model is therefore proposed in which CFS is one of the many manifestations of zoster sine herpete; that is, herpes zoster without rash. Furthermore, re-exposure to VZV in the form of chickenpox has become less common in the past few decades; without such re-exposure, immunity to VZV drops, which could explain the increased incidence of CFS. Co-infection with multiple herpesviruses is a possibility, as some CFS patients show signs of infection with other herpesviruses including Epstein-Barr, Cytomegalovirus, and HHV6. These three herpesviruses can attack immune cells, and may therefore promote neurotropic herpesvirus reactivation in the ganglia.

The possibility of VZV as the causal agent in CFS has previously received almost no attention; the possibility that CFS involves infection of the peripheral ganglia has likewise been largely overlooked. This suggests that the search for a viral cause of CFS has been far from exhaustive. Several antiherpes drugs are available, as is a vaccine for VZV; more research into such agents as possible treatments for CFS is urgently needed.

 

Source: Shapiro JS. Does varicella-zoster virus infection of the peripheral ganglia cause Chronic Fatigue Syndrome? Med Hypotheses. 2009 Nov;73(5):728-34. doi: 10.1016/j.mehy.2009.04.043. Epub 2009 Jun 10. https://www.ncbi.nlm.nih.gov/pubmed/19520522

 

Detection of herpesviruses and parvovirus B19 in gastric and intestinal mucosa of chronic fatigue syndrome patients

Abstract:

BACKGROUND: Human herpesvirus-6 (HHV-6), Epstein-Barr virus and parvovirus B19 have been suggested as etiological agents of chronic fatigue syndrome but none of these viruses is consistently detected in all patients. However, active viral infections may be localized in specific tissues, and, therefore, are not easily detectable. The aim of this study was to investigate the presence of HHV-6, HHV-7, EBV and parvovirus B19 in the gastro-intestinal tract of CFS patients.

PATIENTS AND METHODS: Using real-time PCR, viral DNA loads were quantified in gastro-intestinal biopsies of 48 CFS patients and 35 controls.

RESULTS: High loads of HHV-7 DNA were detected in most CFS and control biopsies. EBV and HHV-6 were detected in 15-30% of all biopsies. Parvovirus B19 DNA was detected in 40% of the patients versus less than 15% of the controls.

CONCLUSION: Parvovirus B19 may be involved in the pathogenesis of CFS, at least for a subset of patients. The gastro-intestinal tract appears as an important reservoir of infection for several potentially pathogenic viruses.

 

Source: Frémont M, Metzger K, Rady H, Hulstaert J, De Meirleir K. Detection of herpesviruses and parvovirus B19 in gastric and intestinal mucosa of chronic fatigue syndrome patients. In Vivo. 2009 Mar-Apr;23(2):209-13. http://iv.iiarjournals.org/content/23/2/209.long (Full article)

 

Chronic fatigue syndrome and complement activation

Abstract:

This report describes a case of chronic fatigue syndrome (CFS) that followed a well-documented episode of acute Epstein-Barr virus (EBV) mononucleosis. All aetiological tests for chronic fatigue were found to be negative or normal, as were immunological tests. After 2 years of chronic fatigue following the acute illness, measurements of complement split products were performed to test for complement activation. These were positive and remained positive for 14 months, after which the patient then recovered from CFS.

 

Source: Geller RD, Giclas PC. Chronic fatigue syndrome and complement activation. BMJ Case Rep. 2009;2009. pii: bcr08.2008.0819. doi: 10.1136/bcr.08.2008.0819. Epub 2009 Mar 17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028106/ (Full article)

 

Is chronic fatigue syndrome caused by a rare brain infection of a common, normally benign virus?

Abstract:

Chronic fatigue syndrome (CFS) is a disabling disease of unknown aetiology. A variety of factors have been suggested as possible causes. Although the symptoms and clinical findings are heterogeneous, the syndrome is sufficiently distinct, at least in relation to the more obvious cases, that a common explanation seems likely. In this paper, it is proposed that the disease is caused by a ubiquitous, but normally benign virus, e.g., one of the circoviruses.

Circoviruses are chronically present in a majority of people, but are rarely tested for diagnostically. Normally these viruses do not penetrate the blood-brain barrier, but exceptions have been reported, and related viruses cause disease in the central nervous system of animals.

The flu-like illness that often precedes the onset of CFS may either suppress immune function, causing an increased viremia, and/or lower the blood-brain barrier. In both cases the result may be that a virus already present in the blood enters the brain. It is well known that zoonotic viruses typically are more malignant than viruses with a long history of host-virus evolution. Similarly, a virus reaching an unfamiliar organ may cause particular problems.

 

Source: Grinde B. Is chronic fatigue syndrome caused by a rare brain infection of a common, normally benign virus? Med Hypotheses. 2008 Aug;71(2):270-4. doi: 10.1016/j.mehy.2008.03.014. Epub 2008 Apr 25. https://www.ncbi.nlm.nih.gov/pubmed/18440157

 

Chronic fatigue syndrome after human parvovirus B19 infection without persistent viremia

Abstract:

BACKGROUND: It is unclear how often chronic fatigue syndrome (CFS) appears after human parvovirus B19 (B19) infection and whether prolonged B19 viremia or some other factors cause CFS.

OBJECTIVES: To determine how often CFS appears after B19 infection and whether prolonged B19 DNA presence, antibody production and persistently reduced complement levels occur in CFS patients after B19 infection.

METHODS: Clinical findings were examined in 210 patients after B19 infection, and CH50, C3 and C4 levels were determined. B19 DNA and antibodies to B19 were also tested in 38 patients’ sera including 3 with CFS.

RESULTS: Serum B19 DNA disappeared after 4-5 months in all 18 patients tested. There are no differences in B19 DNA-positive period between patients with and without persistent symptoms. IgM antibody titers to B19 became reduced after 2 months in all 38 patients. Complement levels persistently decreased in a greater proportion of patients with persistent symptoms.

CONCLUSIONS: The present study suggests that we should consider the possibility of CFS after B19 infection and that CFS may be derived from several aspects other than prolonged B19 DNA presence in sera.

Copyright 2008 S. Karger AG, Basel.

 

Source: Seishima M, Mizutani Y, Shibuya Y, Arakawa C. Chronic fatigue syndrome after human parvovirus B19 infection without persistent viremia. Dermatology. 2008;216(4):341-6. doi: 10.1159/000116723. Epub 2008 Feb 15. https://www.ncbi.nlm.nih.gov/pubmed/18277075

 

Immunoassay with cytomegalovirus early antigens from gene products p52 and CM2 (UL44 and UL57) detects active infection in patients with chronic fatigue syndrome

Abstract:

AIMS: To investigate whether the use of recombinant early antigens for detection of antibodies to human cytomegalovirus (HCMV) gene products CM(2) (UL44, UL57) and p52 (UL44) is specific in the diagnosis and differentiation of active HCMV infection in a subset of patients with chronic fatigue syndrome (CFS), a diagnosis which is often missed by the current ELISA assay that uses crude viral lysate antigen.

METHODS: At a single clinic from 1999 to 2001, a total of 4774 serological tests were performed in 1135 patients with patients using two immunoassays, Copalis and ELISA. The Copalis immunoassay utilised HCMV early gene products of UL44 and UL57 recombinant antigens for detection of HCMV IgM antibody, and viral capsid antigen for detection of HCMV IgG antibody. The ELISA immunoassay utilised viral crude lysate as antigen for detection of both HCMV IgG and IgM.

RESULTS: 517 patients (45.6%) were positive for HCMV IgG by both assays. Of these, 12 (2.2%) were positive for HCMV(V) IgM serum antibody by HCMV ELISA assay, and 61 (11.8%) were positive for IgM HCMV serum antibody by Copalis assay. The Copalis assay that uses HCMV early recombinant gene products CM(2) (UL44, UL57) and p52 (UL44) in comparison with ELISA was 98% specific.

CONCLUSIONS: Immunoassays that use early antigen recombinant HCMV CM(2) and p52 are five times more sensitive than HCMV ELISA assay using viral lysate, and are specific in the detection and differentiation of active HCMV infection in a subset of patients with CFS.

 

Source: Beqaj SH, Lerner AM, Fitzgerald JT. Immunoassay with cytomegalovirus early antigens from gene products p52 and CM2 (UL44 and UL57) detects active infection in patients with chronic fatigue syndrome. J Clin Pathol. 2008 May;61(5):623-6. Epub 2007 Nov 23. https://www.ncbi.nlm.nih.gov/pubmed/18037660

 

Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach

Abstract:

BACKGROUND AND AIMS: The aetiology for chronic fatigue syndrome (CFS) remains elusive although enteroviruses have been implicated as one of the causes by a number of studies. Since most CFS patients have persistent or intermittent gastrointestinal (GI) symptoms, the presence of viral capsid protein 1 (VP1), enterovirus (EV) RNA and culturable virus in the stomach biopsy specimens of patients with CFS was evaluated.

METHODS: 165 consecutive patients with CFS underwent upper GI endoscopies and antrum biopsies. Immunoperoxidase staining was performed using EV-specific monoclonal antibody (mAb) or a control mAb specific for cytomegalovirus (CMV). RT-PCR ELISA was performed on RNA extracted from paraffin sections or samples preserved in RNA later. Biopsies from normal stomach and other gastric diseases served as controls. 75 samples were cultured for EV.

RESULTS: 135/165 (82%) biopsies stained positive for VP1 within parietal cells, whereas 7/34 (20%) of the controls stained positive (p< or =0.001). CMV mAb failed to stain any of the biopsy specimens. Biopsies taken from six patients at the onset of the CFS/abdominal symptoms, and 2-8 years later showed positive staining in the paired specimens. EV RNA was detected in 9/24 (37%) paraffin-embedded biopsy samples; 1/21 controls had detectable EV RNA (p<0.01); 1/3 patients had detectable EV RNA from two samples taken 4 years apart; 5 patient samples showed transient growth of non-cytopathic enteroviruses.

CONCLUSION: Enterovirus VP1, RNA and non-cytopathic viruses were detected in the stomach biopsy specimens of CFS patients with chronic abdominal complaints. A significant subset of CFS patients may have a chronic, disseminated, non-cytolytic form of enteroviral infection, which could be diagnosed by stomach biopsy.

Comment in: Enterovirus infection of the stomach in chronic fatigue syndrome/myalgic encephalomyelitis. [J Clin Pathol. 2008]

 

Source: Chia JK, Chia AY. Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach. J Clin Pathol. 2008 Jan;61(1):43-8. Epub 2007 Sep 13. https://www.ncbi.nlm.nih.gov/pubmed/17872383