By David Tuller, DrPH

Carol Monaghan, a member of Parliament from the Glasgow area, has done it again. This week she is spearheading a three-hour debate in the House of Commons about the awful situation confronting ME patients in the UK. (The organizers of this debate are using ME, not CFS or ME/CFS or CFS/ME. As readers know, the issue of what to call the disease or cluster of diseases is fraught.)

This will be the third parliamentary debate she has organized in the last year. The difference this time around is that the debate will be held in the House of Commons itself, not in Westminster Hall like the first two. House of Commons debates are a much bigger deal. They tend to receive more press attention and have a greater potential impact on policy developments going forward. They also allow for a vote on a motion put forward by the organizers. (Of course, given Brexit insanity, it’s unclear how much coverage anything else will get, just as Trump insanity overwhelms every other issue in U.S. news coverage.)

The first two debates were held in February and June. In these initial forays, Monaghan focused on the PACE trial, among other issues. In doing so, she provided the single most damning quote about the study that I’ve heard from anyone in UK politics. “I think that when the full details of the trial become known, it will be considered one of the biggest medical scandals of the 21st century,” she declared. 

(I have suggested that this claim is too modest. When the full details become known, it could be considered one of the biggest medical scandals of the millennium—even though the millennium is only 19 years old.)

Along with three other MPs, Monaghan presented her case for the new debate in late October. More than 30 MPs overall supported the call for the House of Commons debate, so the push is a cross-party affair, not a partisan issue. Apparently members from across the political spectrum have recognized the stunning failures of the UK medical and academic establishments in this particular situation. Many undoubtedly became aware of the problems through contact with constituents suffering from the illness, which is how Monaghan stumbled onto it. Before that, she said, she knew next to nothing about the issue or about the PACE trial.

(Here is a Q-and-A with Carol Monaghan I posted last March.)

The motion proposed for consideration touches multiple important bases. Here it is:

“That this House calls on the Government to provide increased funding for biomedical research into the diagnosis and treatment of ME, supports the suspension of Graded Exercise Therapy and Cognitive Behaviour Therapy as means of treatment, supports updated training of GPs and medical professionals to ensure they are equipped with clear guidance on diagnosis of ME and appropriate management advice to reflect international consensus on best practice, and is concerned about the current trends of subjecting ME families to unjustified child protection procedures.”

In addition to these critical issues, it is my hope that one of the presenting MPs specifically calls out both the University of Bristol for its scientifically invalid research into pediatric manifestations of the illness and BMJ for publishing these bogus studies. I have documented over and over that this research violates multiple core methodological and ethical principles and should never have been published in the first place. Yet instead of taking action to correct the scientific record, BMJ has stonewalled and, in some instances, conveyed false information or absurd arguments in its defense. The Bristol University vice chancellor, for his part, has filed multiple complaints with Berkeley to try to shut me up. That obviously hasn’t worked.

TWiV 531: Circ du RNA

Patrick Moore returns to TWiV to discuss the discovery from the Chang-Moore laboratory of circular RNAs in cells infected with herpesviruses.

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RNA in circles

circRNAThe diversity of cellular RNA structure and function has progressed from the early days of molecular biology, when we thought only about mRNA, tRNA and ribosomal RNAs. Then RNA splicing was discovered along with the many small nuclear RNAs that mediate that process. Next came small interfering RNAs and microRNAs and long noncoding RNAs, master regulators of cell processes. The latest addition to the RNA toolbox are circular RNAs (circRNA), first found in viroids, then cells, and now encoded in the genomes of two herpesviruses.

Circular RNAs were first found to constitute the genetic information of viroids, unusual pathogens of plants that encode no protein. Later circular RNAs were found in uninfected cells, where they are produced by backsplicing: a downstream 5’-splice donor joins an upstream 3’-splice acceptor (illustrated). They have a number of diverse functions in cells, including acting as miRNA sponges, sequestering miRNAs so that they cannot degrade target mRNAs; regulating transcription, splicing, translation, and ribosomal RNA processing, and acting as adaptors for protein-protein interactions. They have been implicated in neuronal and cardiovascular diseases and cancer.

Circular RNAs have recently been discovered in cells infected with two different DNA tumor viruses, Epstein-Barr virus (EBV) and Kaposi’s sarcoma herpesvirus (KSHV). These two herpesviruses account for about 2% of all human cancers, including lymphoid and non lymphoid malignancies (EBV), Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease (KSHV). Outbreaks of Kaposi’s sarcoma in the US in the early 1980s were the first signs of the emergence of a new immunosuppressive disease, AIDS, caused by HIV-1.

circRNAs from several regions of the EBV genome were detected in infected cells and in post transplant lymphoproliferative disease, Burkitt lymphoma, nasopharyngeal carcinoma, and AIDS-associated lymphoma. circRNAs were also detected in some KSHV infected primary effusion lymphoma cell lines and from some (but not all) Kaposi’s sarcomas.

The contribution of these newly discovered viral circRNAs to tumorigenesis is unknown. One type of circRNA was found in all EBV-associated tumors examined, suggesting that at least for these cancers, they might have some role in tumor development or maintenance. Because circRNAs are very resistant to exonuclease degradation, they might be more useful than viral DNA detection for predicting disease.

I wonder how many other DNA viruses encode circRNAs in their genomes, and what are their contributions to viral replication and pathogenesis.

TWiV 530: Quiet please!

Steve Goff returns to TWiV to discuss the work of his laboratory on how retroviral genomes are silenced in infected cells.

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Toll to the Rescue

prion conversionby Gertrud U. Rey

Transmissible spongiform encephalopathies (TSEs) include a variety of fatal neurodegenerative diseases caused by infectious proteins called prions. Although prions are not viruses, their ability to self-propagate without a nucleic acid intermediate has always fascinated virologists, causing them to adopt prions into their repertoire of pathogenic agents. Common TSEs comprise scrapie in sheep, bovine spongiform encephalopathy (“mad cow disease”) in cattle, Creutzfeld-Jakob disease in humans, and chronic wasting disease in deer.

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TWiV 529: Rueckert Road

At the University of Wisconsin-Madison, Vincent meets up with one of his virology heroes, Roland R. Rueckert, to talk about his research and his second career as a forest manager.

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By David Tuller, DrPH

I was surprised recently when the UK press made a big splash about what was, in the end, a modest study from a team led by Carmine Pariante, a professor of psychiatry at Kings College London. I was less surprised when I realized that the Science Media Centre was involved in disseminating the news. The coverage generated by the SMC’s efforts largely paralleled the overblown claims made by the study authors themselves in linking this paper about hepatitis C patients to possible biological mechanisms underlying what they call “chronic fatigue syndrome.” (The same illness or cluster of related illnesses is also referred to as myalgic encephalomyelitis, CFS/ME and ME/CFS, among other names.)

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By David Tuller, DrPH

Alan Montgomery is a professor of medical statistics and clinical trials at the University of Nottingham’s School of Medicine. He is also the senior author of the Lightning Process study published in 2017 in Archives of Disease in Childhood, a BMJ journal. Professor Montgomery formerly worked at University of Bristol, along with Professor Esther Crawley and the other co-authors of the Lightning Process study.

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In the first episode for 2019, the TWiV team reviews the amazing virology stories of the past year.

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We did a lot of science communication in 2018. By we, I mean all the individuals who gave their time selflessly to write for this blog or record podcasts with me. Here is a summary of what we did last year.

virology blog

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