Retrotransposons shuttling genetic and epigenetic information from the nuclear to the mitochondrial compartment: Do they play a pathogenetic role in scleroderma?

Abstract

Endogenous retroelements are a class of ancient defective viral insertions contained in the genome of host cells, where they account for up to 40% of all DNA. Centuries of co-existence in host genome have led to the development of immunotolerance to endogenous retroelements, most of which are defective and unable to replicate or transcribe functional proteins. However, given their capacity to move across the nuclear and mitochondrial genome and recombine, they could mix phenotypes and give rise to infections that may trigger innate and adaptive immune responses by sensing receptors capable of recognising foreign nucleic acids and proteins. It has recently been suggested that they play a role in the pathogenesis of autoimmune diseases on the grounds of their partial reactivation or the epigenetic control of host gene transcription. A number of studies have confirmed their contribution to the development of rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus, but there is still a lack of data concerning systemic sclerosis (SSc). Their role in the pathogenesis of SSc can be hypothesised on the basis of mitochondrial and nuclear chromatinic damage, and hyper-activation of the immune pathway involved in antiviral defense. SSc is characterised by genetic and immunological evidence of a viral infection but, as no viral agent has yet been isolated from SSc patients, the hypothesis that partial reactivation of endogenous retroviruses may trigger the disease cannot be excluded and deserves further investigation.

• Authors: Rossella Talotta, Piercarlo Sarzi-Puttini, Magdalena Janina Laska, Fabiola Atzeni
• Journal: Cytokine & growth factor reviews (Cytokine Growth Factor Rev) Vol. 49 Pg. 42-58 (10 2019) ISSN: 1879-0305 [Electronic] England
• PMID: 31677967 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Retroelements

Topics

• Adaptive Immunity
• Animals
• Autoimmune Diseases (genetics, immunology)
• Cell Nucleus (genetics, metabolism)
• Clinical Trials as Topic
• Epigenesis, Genetic
• Humans
• Immunity, Innate
• Mice
• Mitochondria (genetics, metabolism)
• Retroelements
• Scleroderma, Systemic (genetics, immunology, virology)
• Transcription, Genetic
• Virus Diseases (immunology)