Endogenous Retroelements and the Host Innate Immune Sensors

Abstract

The ability to distinguish between self and nonself is the fundamental basis of the immune system in all organisms. The conceptual distinction between self and nonself, however, breaks down when it comes to endogenous retroviruses and other retroelements. While some retroelements retain the virus-like features including the capacity to replicate and reinvade the host genome, most have become inactive through mutations or host epigenetic silencing. And yet, accumulating evidence suggests that endogenous retroelements, both active and inactive, play important roles not only in pathogenesis of immune disorders, but also in proper functioning of the immune system. This review discusses the recent development in our understanding of the interaction between retroelements and the host innate immune system. In particular, it focuses on the impact of retroelement transcripts on the viral RNA sensors such as Toll-like receptors, RIG-I-like receptors, protein kinase R, and the inflammasomes.

RIG-I: a multifunctional protein beyond a pattern recognition receptor

“…A positive feedback is ultimately released to facilitate IgM production (Zeng et al, 2014 ). Besides, SINEs could also function as endogenous ligands for RIG-I when the SINEs are transcribed by polymerase III under cellular and environmental stresses (Mu et al, 2016 ).

Figure 1 Various RNA ligands and post-translational regulations of RIG-I .

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Novel endogenous simian retroviral integrations in Vero cells: implications for quality control of a human vaccine cell substrate

“…Although mammalian genomes contain numerous copies of retrovirus-related sequences, most ERVs in the mammalian genome are inactive, functioning as neither transposable elements nor infectious agents 23 – 25 , 28 . However, ERVs may sometimes inactivate or activate nearby genes in the host cell genome, while the transcribed RNA of ERVs may directly activate the innate immune system of host cells 24 , 28 , 29 . In addition, ERVs may have cryptic potential to generate infectious virus particles after recombination or mutual complementation among different inactive proviruses 24 , 25 , 27 .…”

RNA Editing and Retrotransposons in Neurology

“…Alu elements (without obvious editing) in the 5′UTR can regulate gene expression (see example with CHNRA6 in chapter 4). The major function of ADAR1-mediated A-to-I editing of inverted-repeat Alus (and perhaps L1; Orecchini et al, 2017a and references therein) in the 3′UTR seems to be suppression (or regulation) of the endogenous IFN-mediated immune response (George et al, 2016 ; Mu et al, 2016 ; Ahmad et al, 2018 ; Chung et al, 2018 ). Thus, endogenous dsRNA structures emerge as a new factor in inflammation and in the context of this manuscript in neuroinflammation.…”