Resurrection of endogenous retroviruses during aging reinforces senescence, 2023, Liu et al

Resurrection of endogenous retroviruses during aging reinforces senescence
Liu X, Liu Z, Wu Z, Ren J, Fan Y, Sun L, Cao G, Niu Y, Zhang B, Ji Q, Jiang X, Wang C, Wang Q, Ji Z, Li L, Esteban CR, Yan K, Li W, Cai Y, Wang S, Zheng A, Zhang YE, Tan S, Cai Y, Song M, Lu F, Tang F, Ji W, Zhou Q, Belmonte JCI, Zhang W, Qu J, Liu GH. R

Whether and how certain transposable elements with viral origins, such as endogenous retroviruses (ERVs) dormant in our genomes, can become awakened and contribute to the aging process is largely unknown.

In human senescent cells, we found that HERVK (HML-2), the most recently integrated human ERVs, are unlocked to transcribe viral genes and produce retrovirus-like particles (RVLPs). These HERVK RVLPs constitute a transmissible message to elicit senescence phenotypes in young cells, which can be blocked by neutralizing antibodies. The activation of ERVs was also observed in organs of aged primates and mice as well as in human tissues and serum from the elderly. Their repression alleviates cellular senescence and tissue degeneration and, to some extent, organismal aging.

These findings indicate that the resurrection of ERVs is a hallmark and driving force of cellular senescence and tissue aging.

Link | PDF (Cell)

 

See also the thread on Temelimab, a monoclonal antibody against a HERV-W glycoprotein, which the Swiss are trialling in long COVID (also being evaluated for MS).

 

A little more on HERVs in MS, which I'll put here in this non-ME thread. Please see also threads tagged with herv.

These are a few background papers relating to the cascade as a hypothetical mechanism in MS. (I think it might be summarised as: "some-virus" or immune challenge -> immune dysregulation -> loss of immune control of latent virus -> EBV/HHV (trans)activation <-> HERV expression -> "badness").

These papers all relate to multiple sclerosis. The first (2021) paper is a comprehensive overview, containing the following —

There's also the interesting suggestion that MS ± various autoimmune conditions could have their female predisposition explained by a pathological HERV incompletely encoded on the X chromosome.

• Cumulative Roles for Epstein-Barr Virus, Human Endogenous Retroviruses, and Human Herpes Virus-6 in Driving an Inflammatory Cascade Underlying MS Pathogenesis (2021, Frontiers in Immunology)
• Do Human Endogenous Retroviruses Contribute to Multiple Sclerosis, and if So, How? (2018, Molecular Neurobiology)
• The aliens inside us: HERV-W endogenous retroviruses and multiple sclerosis (2018, Multiple Sclerosis Journal)
• Epstein-Barr Virus-Induced Genes and Endogenous Retroviruses in Immortalized B Cells from Patients with Multiple Sclerosis (2022, Cells)
• Expression and activation by Epstein Barr virus of human endogenous retroviruses-W in blood cells and astrocytes: inference for multiple sclerosis (2012, PLOS One)

I wonder whether this MS-related research could relate to ME/LC. Conceivably that MS end-point might be a genetically or otherwise determined fork in the road (maybe depending on things like HLA or the specific HERV), where an alternative result could be ME/CFS (or ALS or Parkinson's or glioblastoma etc).