SARS-CoV-2 awakens ancient retroviral genes and the expression of proinflammatory HERV-W envelope protein in COVID-19 patients, 2023, Charvet et al.

[Arvo]

At this point it's still a preprint.

Abstract:

Patients with COVID-19 may develop abnormal inflammatory response and lymphopenia, followed in some cases by delayed-onset syndromes, often long-lasting after the initial SARS-CoV-2 infection. As viral infections may activate human endogenous retroviral elements (HERV), we studied the effect of SARS-CoV-2 on HERV-W and HERV-K envelope (ENV) expression, known to be involved in immunological and neurological pathogenesis of human diseases. Our results have showed that the exposure to SARS-CoV-2 virus activates early HERV-W and K transcription but only HERV-W ENV protein expression, in an infection- and ACE2-independent way within peripheral blood mononuclear cell cultures from one-third of healthy donors. Moreover, HERV-W ENV protein was significantly increased in serum and plasma of COVID-19 patients, correlating with its expression in CD3+ lymphocytes and with disease severity. Finally, HERV-W ENV was found expressed in post-mortem tissues of lungs, heart, brain olfactory bulb and nasal mucosa from acute COVID-19 patients in cell-types relevant for COVID-19-associated pathogenesis within affected organs, but different from those expressing of SARS-CoV-2 antigens. Altogether, the present study revealed that SARS-CoV-2 can induce HERV-W ENV expression in cells from individuals with symptomatic and severe COVID-19. Our data suggest that HERV-W ENV is likely to be involved in pathogenic features underlying symptoms of acute and post-acute COVID. It highlights the importance to further understand patients’ genetic susceptibility to HERV-W activation and the relevance of this pathogenic element as a prognostic marker and a therapeutic target in COVID-19 associated syndromes.

As most of you know, in the 80s researchers were excited about several (and separate) finds of retroviral activity in what we now call ME/CFS patients. The main researcher was Elaine DeFreitas, whose finds got dismissed by UK reserachers Behan and Gow as finding only "harmless" endogenous retrovirus.

DeFreitas insisted that they had been sloppy and didn't replicate her lab methods properly.

Either way, retroviral activity was undeniably present, and under certain circumstances endogenous retrovirus appears not to be harmless at all.

According to a quick wikipedia search:


Neurology, immunity, cancer: same cluster of stuff as where ME/CFS can be found. I was stricken by the presence of both multiple sclerosis (MS) and schizophrenia, as these are àlso associated with Epstein Barr virus (EBV), just as ME/CFS and Long COVID are.


If I hadn't coïncidentally been reminded of the 80s retroviral finds being dismissed as endogenous yesterday in Osler's web (because I was trying to find something else), I might have missed the connection.


https://www.medrxiv.org/content/10.1101/2022.01.18.21266111v2

 

[Arvo]

Two twitter threads about the paper:



and

 

[Arvo]

If it turns out to be a major factor in ME/CFS, then "zombie virus" is accurate on multiple levels



Also, there was a study with similar finds published in the Lancet:



Link to study: Evidence of the pathogenic HERV-W envelope expression in T lymphocytes in association with the respiratory outcome of COVID-19 patients - eBioMedicine (thelancet.com)

 

[Arvo]

Thanks @Cheshire /mod team for adding the link to the actual paper!

I had retrieved it, but I'm unfortunately having very increased scatterbrain atm, really glad you added it for me.

 

[SNT Gatchaman]

Merged thread - final paper

SARS-CoV-2 awakens ancient retroviral genes and the expression of proinflammatory HERV-W envelope protein in COVID-19 patients
Benjamin Charvet; Joanna Brunel; Justine Pierquin; Mathieu Iampietro; Didier Decimo; Nelly Queruel; Alexandre Lucas; María del Mar Encabo-Berzosa; Izaskun Arenaz; Tania Perez Marmolejo; Arturo Ivan Gonzalez; Armando Castorena Maldonado; Cyrille Mathieu; Patrick Küry; Jose Flores-Rivera; Fernanda Torres-Ruiz; Santiago Avila-Rios; Gonzalo Salgado Montes de Oca; Jon Schoorlemmer; Hervé Perron; Branka Horvat

Patients with COVID-19 may develop abnormal inflammatory response, followed in some cases by severe disease and long-lasting syndromes. We show here that in vitro exposure to SARS-CoV-2 activates the expression of the human endogenous retrovirus (HERV) HERV-W proinflammatory envelope protein (ENV) in peripheral blood mononuclear cells from a subset of healthy donors, in ACE2 receptor and infection-independent manner.

Plasma and/or sera of 221 COVID-19 patients from different cohorts, infected with successive SARS-CoV-2 variants including the Omicron, had detectable HERV-W ENV, which correlated with ENV expression in T-lymphocytes and peaked with the disease severity. HERV-W ENV was also found in post-mortem tissues of lungs, heart, gastrointestinal tract, brain olfactory bulb and nasal mucosa from COVID-19 patients.

Altogether, these results demonstrate that SARS-CoV-2 could induce HERV-W envelope protein expression and suggest its involvement in the immunopathogenesis of certain COVID-19-associated syndromes and thereby its relevance in the development of personalized treatment of patients.

Link | PDF (Cell/iScience)

 

[Hutan]

HERV abnormal expression may also become self-sustained, thus creating chronic protein expression in affected tissues, e.g., with cytokine-mediated feedback loops.17 Such a sustained expression has been shown to be involved in brain lesions with lifelong expansion in patients with multiple sclerosis (MS).15,18,19

?

HERV envelope proteins can be inserted in cell membranes but may also be released extracellularly. Some of them were shown to exert major immunopathogenic 20-23 and/or neuropathogenic 19,24
effects in vitro and in vivo, associated with disease pathognomonic features.

SARS-CoV-2 triggers HERV-W and -K ENV mRNA early transcription along with HERV-W ENV protein in peripheral blood mononuclear cells (PBMC) of healthy donors
The interesting thing in this section was not so much that exposure of healthy leukocytes to SARS-CoV-2 resulted in transcription of the HERV mRNA, but that the effect varied with leukocytes from different donors. It seemed that some people's leukocytes activated the HERVs, and some didn't.

There was further variation in the expression of ENV protein from the mRNA - 3/8 donor samples showed expression of HERV-W protein with exposure to SARS-CoV-2, although in one there was lots, and another there was only a little.

So, it seems that something about donors, their genetics or something else, is causing very different reactions of their leukocytes to HERVs in the presence of the virus.

Exposure to SARS-CoV-2 was necessary for mRNA transcription and expression of HERV protein. And it sounds as though the researchers did multiple exposures to check that the results were consistent.

 

[CRG]

"Affiliations
GeNeuro Innovation"

https://www.geneuro.com/en/technologies/rationale

"Stopping the progression of autoimmune diseases

GeNeuro is pursuing a novel approach for treating autoimmune diseases by seeking to block mechanisms suspected of participating to their onset and development. This approach is the result of 30 years of research into human endogenous retroviruses (HERVs), including 15 years within the Institut Mérieux group and INSERM, before GeNeuro was founded in 2006."