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Review
, 24 (6), 692-7

Endogenous Retroelements and Autoimmune Disease

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Review

Endogenous Retroelements and Autoimmune Disease

Daniel B Stetson. Curr Opin Immunol.

Abstract

Innate immune sensors of foreign nucleic acids are essential for antiviral immunity, but these same sensors can cause autoimmune disease through inappropriate detection of self-nucleic acids. The sources of the endogenous RNA and DNA that trigger autoreactive responses include chromatin and ribonucleoproteins that are the targets of autoantibodies in numerous autoimmune diseases, including systemic lupus erythematosus. In this review, I discuss recent data implicating endogenous retroelements-viruses that make up a substantial fraction of our genomes-as an important source of endogenous nucleic acids that can cause autoimmune disease. Understanding this potentially pathologic role for retroelements and the precise mechanisms by which their genomes are sensed and metabolized has important implications for the diagnosis and treatment of numerous autoimmune disorders.

Figures

Figure 1
Figure 1
AGS genes cooperate to metabolize reverse transcription products of endogenous retroelements. A schematic of the retroviral reverse transcription process is shown. SAMHD1, an AGS gene and HIV-1 restriction factor, prevents the initiation of reverse transcription by controlling dNTP availability to RT enzymes. A speculative role for RNaseH2 in degrading the RNA strand of RNA/DNA hybrids is depicted. Trex1 can block retrotransposition by metabolizing the reverse-transcribed DNA of retroelements. Failure to metabolize these viral nucleic acids may trigger the ISD pathway through accumulation of RNA/DNA hybrids or reverse-transcribed DNA.

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