Solve ME/CFS Initiative: 2018 Ramsay Class Receives Supplemental Funding to Support Innovative Projects from New Investigators

Andy · Dec 22, 2018

Funding awarded to promising new studies led by Dr. Dawei Li and Dr. Malav Trivedi

“Endogenous retroviruses (ERVs) and their expression in chronic fatigue syndrome”, Primary Investigator: Assistant Professor Dawei Li, University of Vermont
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“ME/CFS In a Petri Dish”, Primary Investigator: Assistant Professor Malav Trivedi, Nova Southeastern University
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http://go.solvecfs.org/webmail/1926...eb2b821c459697133845373a35af1590d299b6891b413

Cinders66 · Dec 23, 2018

Does this mean retroviruses are back on the table?

wigglethemouse · Jan 27, 2021

Dawei Li from the University of Vermont has translated his Ramsay Award work into a new R21 NIH Grant of $248,289 to study "Endogenous Retrovirus Analyses In Myalgic Encephalomyelitis"
https://projectreporter.nih.gov/project_info_details.cfm?aid=10196513&icde=31258613

Project Summary/Abstract
Myalgic encephalomyelitis (ME) is a disabling and complex disease with 1-2.5 million patients in the United States. ME patients have low quality of life and one in four are bed- or house-bound. ME is under-studied and under-funded, and there are no existing diagnostic tests, FDA-approved treatments or cure for ME. The causes of ME are unknown. ME patients exhibit elevated immune responses and enhanced inflammation.

Endogenous retroviruses (ERVs) result from the fixation of ancient retroviral infections and integrations into the human genome. ERVs (n˜400,000) typically remain silenced; however, some ERVs can be transcriptionally reactivated. Activated ERVs resemble viral RNA and can therefore trigger immune responses and chronic inflammation, potentially leading to ME.

Together with our collaborators, we have collected the largest deep sequencing data sets with deep phenotypes from ME patients. We recently developed a set of bioinformatics tools that allow us to genotype genome-wide individual ERVs and quantify individual ERV expression with high accuracy.

With this R21 application, we propose to use these state-of-the-art tools to analyze existing and new deep sequencing data to address two Specific Aims.

Aim 1: Identify distinct ERVs whose expression is associated with ME using RNA-Sequencing data. These analyses will, for the first time, quantify transcriptome- wide expressed ERVs individually; and allow for identification of activated distinct ERVs and ERV genes associated with ME.

Aim 2: Identify ERV variants whose genotypes are associated with ME using whole- genome sequencing data.

These analyses will produce genome-wide distinct ERV genotypes, and, for the first time, allow for identification of ME-associated individual ERVs and related genes. Upon completion of these two Aims, we will know whether ERVs and ME are linked at the transcriptomic and/or genomic level. Elucidating ERVs as risk factors in ME may lead to breakthroughs in ME treatment, such as repurposing existing FDA-approved anti-retroviral drugs which may reverse ERV effects.
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wigglethemouse · Jan 28, 2021

wigglethemouse said: ↑

Dawei Li from the University of Vermont
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Dawei Li will be moving from University of Vermont to Florida Atlantic University this year.

For background this was his previous smaller 2019/2020 R03 grant.
Comprehensive Analyses Of Endogenous Retroviruses With Severe Chronic Fatigue Syndrome
https://projectreporter.nih.gov/project_info_description.cfm?aid=9962295&map=y

Project Summary/Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (referred to as CFS) is a debilitating disease characterized by unrelenting fatigue, post-exertional malaise, cognitive impairment, sleep problems, and pain. CFS disables 1-2.5 million Americans, and costs $17–24 billion annually. Clinical tests of CFS patients are typically normal. There are currently no molecular biomarkers or FDA-approved treatments. The cause of CFS is unknown. Recent data from ourselves and others show that CFS is a complex and misunderstood disease.

This proposal is aimed at helping to understand the role of endogenous retrovirus (ERV) variations in the genetic predisposition for CFS. We propose a novel CFS model: polymorphic ERV insertions can be activated through demethylation, infectious agents, or both, and the resembled viral RNA triggers the inflammation pathway, ultimately leading to CFS.

The co-contribution of genome-wide ERV variations and their activators is an unexplored research frontier and an important area for research in CFS. Here, we will focus on analyzing existing CFS genome, methylome, transcriptome, and microbiome data to identify ERV variations associated with CFS.

Verifying ERV as a risk factor in CFS will aid in adoption of an antiviral or anti-inflammatory treatment or anti-inflammatory lifestyle. If ERV activators, such as demethylation or infectious agent triggers, are also found, research on this will eventually lead to new therapeutic intervention and prevention.
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Ravn · Feb 2, 2024

wigglethemouse said: ↑

Dawei Li from the University of Vermont has translated his Ramsay Award work into a new R21 NIH Grant of $248,289 to study "Endogenous Retrovirus Analyses In Myalgic Encephalomyelitis"
https://projectreporter.nih.gov/project_info_details.cfm?aid=10196513&icde=31258613
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None of the links above are working for me but this presentation by Dawai Li looks to be related:
“Endogenous Retroviruses and ME/CFS” (starts at 42min)

A few bits from memory (so no guarantee for accuracy):

they developed new, better method of identifying ERVs

presents some unpublished data from several small studies

number of copies of ERV gene relates to circulating cytokines

some ERVs unique to patients

ERV expression in exercise study differs between cases and controls

many of the ERVs found are novel so not known what they do

similar findings in US and EU cohort

ERVs better at predicting disease status than associated human genes

Presentation is part of the December 18, 2023, CDC's 22nd ME/CFS Stakeholder Engagement and Communication (SEC) Call

https://www.youtube.com/watch?v=V1YJE5kgjHs

wigglethemouse · Feb 2, 2024

Ravn said: ↑

None of the links above are working for me
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This is the NIH grant. The NIH Reporter system changed which is probably why the old link didn't work.
https://reporter.nih.gov/search/vgEVcnOE5k2IRs2byslACg/project-details/10888595

Dawei Li has changed Universities a few times. I imagine it can be tough to find somewhere that supports your work. I admire his dedication.

Ravn · Feb 3, 2024

Ah, that link worked. Thanks @wigglethemouse

So the Project End Date is 01-May-2024

Which means the data presented in the video is probably close to complete. Has anyone else had a chance to look it?

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