An HERV-W ENV transcription in atypical memory B cells linked to … risk for [LC] can express the encoded protein from … chromosome X, 2024, Brunel+

[SNT Gatchaman]

Now published - see here
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An HERV-W ENV transcription in atypical memory B cells linked to COVID-19 evolution and risk for long COVID can express the encoded protein from a ribosome readthrough of mRNA from chromosome X.
Joanna Brunel; Julien Paganini; Melissa Galloux; Benjamin Charvet; Herve Perron

The human genome comprises 8% of endogenous retroviruses (HERVs). Though HERVS contribute to physiological functions, copies retained pathogenic potential.

The HERV-W ENV protein was shown expressed in patients with worse COVID-19 symptoms and post-COVID syndrome. A significant detection of the mRNA encoding HERV-W ENV from patients with COVID-19 in B cells from RNAseq reads obtained from peripheral blond mononuclear cells. This data stratified with increased COVID-19 symptoms or with post-acute sequelae of COVID-19 (long COVID) after 3 months.

The HERV-W ENV-U3R RNA was confirmed to display the best alignment with chromosome X ERVWE2 locus. However, a stop codon precluding its translation was re-addressed after recent understandings of ribosome readthrough mechanisms. Experimental results evidenced that this HERV gene can effectively express a full-length protein in the presence of molecules allowing translation via a readthrough mechanism at the ribosome level.

Results not only confirm HERV-W ENV RNA origin in these patients, but show for the first time how a defective HERV copy can be translated into a complete protein when specific factors make it possible at the ribosome level. The present proof of concept now requires further studies to identify the factors involved in this newly understood mechanism, following SARS-CoV-2 exposure.


Link | PDF (Preprint: MedRxiv) [Open Access]

 

[SNT Gatchaman]

(A bit of nominative determinism with the senior author).

See our previous threads —

SARS-CoV-2 awakens ancient retroviral genes and the expression of proinflammatory HERV-W envelope protein in COVID-19 patients (2023, iScience)

HERV-W ENV antigenemia and correlation of increased anti-SARS-CoV-2 immunoglobulin levels with post-COVID-19 symptoms (2022, Frontiers in Immunology)

 

[SNT Gatchaman]

Note however, the failure of temelimab, targeting HERV-W —

The GNC-501 clinical trial is a Phase 2 study in patients suffering from post-COVID-19 neuropsychiatric syndromes, testing temelimab against placebo. The study enrolled over 200 patients in Switzerland, Spain and Italy who had tested positive for HERV-W ENV. The top-line results from this study show that treated patients had no clinically meaningful improvement compared to placebo on the primary endpoint measuring the improvement of fatigue with the PROMIS SF7a test. The majority of secondary endpoints did not show an effect either. The treatment was very well tolerated and safe, consistent with previous clinical trials in other indications.

Also noted in this thread.

 

[SNT Gatchaman]

Now published as —

HERV-W ENV transcription in B cells predicting symptomatic COVID-19 and risk for long COVID can express a full-length protein despite stop codon in mRNA from chromosome X via a ribosome readthrough.
Brunel; Paganini; Galloux; Charvet; Perron

The human genome comprises 8% of endogenous retroviruses (HERVs). Though HERVS contribute to physiological functions, copies retained pathogenic potential. The HERV-W ENV protein was shown expressed in patients with worse COVID-19 symptoms and post-COVID syndrome. A significant detection of the mRNA encoding HERV-W ENV from patients with COVID-19 in B cells from RNAseq reads obtained from peripheral blond mononuclear cells. This data stratified with increased COVID-19 symptoms or with post-acute sequelae of COVID-19 (long COVID) after 3 months. The HERV-W ENVU3R RNA was confirmed to display the best alignment with chromosome X ERVWE2 locus. However, a stop codon precluding its translation was re-addressed after recent understandings of ribosome readthrough mechanisms. Experimental results evidenced that this HERV gene can effectively express a full-length protein in the presence of molecules allowing translation via a readthrough mechanism at the ribosome level.

Results not only confirm HERV-W ENV RNA origin in these patients but show for the first time how a defective HERV copy can be translated into a complete protein when specific factors make it possible at the ribosome level. The present proof of concept now requires further studies to identify the factors involved in this newly understood mechanism, following SARS-CoV-2 exposure.

Link (Microbes and Infection)