Does inflammation cause the reactivation of endogenous retroviruses, some with pathological potential?

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 From Perplexity A.I.

Does inflammation cause the reactivation of endogenous retroviruses, some with pathological potential?
Yes, inflammation can cause the reactivation of endogenous retroviruses (ERVs), and some of these reactivated ERVs have pathological potential.

Multiple studies and reviews support a bidirectional relationship between inflammation and ERV expression:

Triggering Reactivation: Inflammatory processes, including those linked to infections, oxidative stress, or microbiota alterations, can remove epigenetic blocks (like DNA methylation) that normally silence ERVs in the genome. Loss of these controls leads to an increase in ERV expression.

Pathogenic Potential: Once reactivated, ERV transcripts and proteins can act as pathogen-associated molecular patterns (PAMPs), triggering the host’s innate immune response via pattern recognition receptors (PRRs) such as TLRs, cGAS, RIG-I, and MDA5. This activation not only drives further inflammation but can also contribute to tissue pathology in chronic diseases.

Vicious Circle: Studies emphasize a “vicious cycle” where inflammation reactivates ERVs, which in turn fuel more inflammation, perpetuating or aggravating pathological conditions. This cycle has been implicated in neurodegenerative diseases, autoimmune disorders, kidney disease, and chronic inflammatory conditions.

Disease Models and Human Pathology: In the brain, aberrant ERV activation triggers neuroinflammation and is associated with neurological and psychiatric disorders. In the kidney, epigenetic derepression of ERVs leads to RIG-I/STING-mediated fibroinflammation. In the skin, the microbiota and diet-induced inflammation can both upregulate specific ERVs, enhancing immune responses and tissue inflammation.

In summary, inflammation is not only capable of reactivating otherwise silenced endogenous retroviruses, but this reactivation can contribute to a pathological cycle of chronic inflammation and disease.

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