New study may link Fibromyalgia to endogenous retroviruses, Chronic Fatigue Syndrome, and AIDS.
5. Conclusions
To the best of our knowledge this is the first study to report increased expression of HERV-K, HERV-H, HERV-W and INF-β and INF-γ levels correlations, in the immune system of FM patients.
Although the levels of these molecules may serve as biomarkers of FM and/or ME/CFS and/or biosensors of TE activation, the RT-qPCR overall estimation approach used in this pilot study may turn unspecific, broadly associating TE activity with neurological and inflammatory processes. Therefore, future efforts evaluating activation of particular HERVs or TE chromosomal sites should more precisely define disease-specific mechanistic information.
Importantly, the model proposed here linking disease-specific epigenome modifications, TE activation, inflammation and an increased risk of cancer in individuals with compromised RNase activity (Figure 6) might be applicable not only to FM and ME/CFS patients but in any individuals with similar molecular disorders.
https://www.mdpi.com/1422-0067/21/4/1366/htm
HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome
Abstract
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFSMS) is an incapacitating chronic disease that dramatically compromise the life quality. The CFS/ME pathogenesis is multifactorial, and it is believed that immunological, metabolic and environmental factors play a role. It is well documented an increased activity of Human endogenous retroviruses (HERVs) from different families in autoimmune and neurological diseases, making these elements good candidates for biomarkers or even triggers for such diseases. Here the expression of Endogenous retroviruses K and W (HERVK and HERVW) was determined in blood from moderately and severely affected ME/CFS patients. HERVK was overexpressed only in moderately affected individuals and HERVW showed no difference. This is the first report about HERVK differential expression in moderate ME/CFS.
https://www.biorxiv.org/content/10.1101/693465v2
HHV-6A infection induces expression of HERV-K18-encoded superantigen
Albert K. Taia, Janos Lukab, Dharam Ablashic, Brigitte T. Huber
published online 08 June 2009.
Abstract
Background
The human endogenous retrovirus K-18 (HERV-K18) encodes a
superantigen that causes deregulation of the immune system. This
provirus is transcriptionally silent, but can be induced by Epstein–Barr
virus (EBV) infection and IFN-α treatment.
Objectives
Since the herpesvirus EBV induces HERV-K18 expression in human B
cells, it was of interest to determine if other herpesviruses would have
similar HERV-K18 transactivation properties. Human herpesvirus
(HHV)-6A, a neurotropic virus associated with multiple sclerosis, was a
logical candidate for these studies.
Study design
HSB2 cells (HHV-6-negative control), HSB2-ML cells (containing latent
HHV-6A genome) and HSB2/HHV-6A cells (HSB-2 cells productively infected
with HHV-6A) were compared for their level of HERV-K18 transcription,
using quantitative RT-PCR.
Results
Latently infected HSB2-ML cells showed a significant increase in
HERV-K18 RNA compared to the control cells. HERV-K18 expression was even
greater in HSB2 cells productively infected with HHV-6A for 78h.
Conclusion
These results imply that HHV-6A, either in latent form or during
acute infection, directly transactivates HERV-K18. This HERV-K18
induction may be mediated through IFN-α that is produced by the
HHV-6A-infected cells. The functional implications of superantigen
expression are discussed.
http://go.solvecfs.org/webmail/192652/94356535/87c16a8a2145a554ca1b9aa9e52436d19254fbdab954f1ba395d445af17546e6
Background of Dawei Li:
http://www.med.uvm.edu/mmg/faculty/primary-faculty/dawei-li-ph-d
Brigitte Huber may have already shown the role of an endogenous virus triggered by HHV-6 in Chronic Fatigue Syndrome.
Ancient Retrovirus May Contribute to Chronic Fatigue Syndrome, Multiple Sclerosis and Autoimmunity
Smoldering Infections of Two Common Viruses EBV and HHV-6 Cause Inherited Retrovirus Genes to Activate
BALTIMORE, MD--(Marketwire - June 23, 2008) - Brigitte Huber, PhD, of the Tufts University
School of Medicine, presented evidence at a medical conference that
suggested that a reactivated ancient retrovirus embedded in the human
genome may be active in chronic fatigue syndrome (CFS) and multiple
sclerosis (MS) patients. Danish scientists at the same conference suggested
that the activation of this retrovirus, dormant in healthy individuals,
could be the reason why autoimmune conditions worsen with viral infections.
Chronic Fatigue Syndrome and Multiple Sclerosis Patients at Increased Risk
From the Effects of HERV-K18 Activation
"Patients with profoundly fatiguing diseases such as MS and CFS may be
particularly susceptible to HERV-K18 activation," said Dr. Huber. The
announcement was made at the International Symposium on Viruses in CFS and
Post-Viral Fatigue, a satellite conference of the 6th International
Conference on HHV-6 & 7. Using an SNP-based genotyping method, Dr. Huber
found that both MS and CFS patients (whose illness had been triggered by
infectious mononucleosis) were at a higher relative risk for containing
HERV-K18 variants known to induce superantigen activity. Superantigens are
proteins that are able to induce a strong undifferentiated T-cell response
believed to deplete the immune system over time.
Viral activity and/or immune activation has been shown to trigger HERV-K18
activity. Both Epstein-Barr virus infection (infectious mononucleosis) and
interferon-alpha administration are associated with HERV-K18 activity.
"HHV-6 activates HERV-K18 as well," said Danish investigator Per Hollsberg,
MD and professor from the University of Aarhus In Denmark. His PhD student
Vanda Lauridsen Turcanova presented this data at the same conference.
"Furthermore, this retrovirus activation may have important consequences
for autoimmunity," he added.
HERV-K18 activation may be the endpoint of an HHV6/EBV interferon pathway
operating in both MS and CFS. HHV-6 is being investigated as a co-factor in
both diseases. Other retroviruses, HERV-H and HERV-W, have been implicated
in MS by other researchers. Over 75% of MS patients meet the criteria for
CFS. Fatigue is often the most disabling symptom for MS patients. The two
diseases also share characteristics such as grey matter atrophy, impaired
cerebral glucose metabolism, autonomic nervous system activity and altered
patterns of brain activity.
Dr. Huber's study suggests that endogenous retroviral activation in CFS and
MS could produce some of the symptoms associated with both diseases. She
has received a National Institutes of Health (NIH) grant to study these
issues. Per Hollsberg has done extensive research on the role of EBV and
HHV-6 in multiple sclerosis.
The HHV-6 Foundation
The HHV-6 Foundation encourages scientific exchanges and provides grants to
researchers seeking to increase our understanding of HHV-6 infection in a
wide array of central nervous system disorders. Daram Ablashi, the
co-discoverer of the HHV-6 virus, is the Foundation's Scientific Director.