The potential role of retroviruses in autoimmunity

Abstract

In the last 20 years research in Immunology underwent fundamental changes. Most importantly, the identification of the key role of innate immune pattern recognition receptors (PRRs) that recognize evolutionarily conserved molecular patterns on infectious pathogens. This results in priming of innate immune cells, which in turn activate and direct the adaptive immune response. Progress in innate immune recognition instigated the current working hypothesis, that recognition of endogenous ligands by PRRs results in innate immune cell activation (autoinflammation) or activation of adaptive cells, with self-reactive antigen receptors (autoimmunity). In particular, nucleic acid-sensing innate immune receptors seem to be prime candidates for a mechanistic understanding of autoreactive activation of the immune system. However, it remains uncertain what the actual source of nucleic acid ligands is and what other signals are needed to drive activation of autoreactive innate immune cells and break self-tolerance of the adaptive immune system. Here, I will review our present understanding about whether the infection with exogenous retroviruses or the reactivation of endogenous retroviruses might play an etiological role in certain autoimmune conditions of humans and murine experimental models.

Regulatory activities of transposable elements: from conflicts to benefits

“…For instance, overexpression of ERV envelope proteins, as seen in the brain of patients affected with some neurodegenerative and autoimmune disorders, can induce a wide range of cellular processes and abnormalities associated with these pathologies, such as neurodegeneration 127 , autoinflammation 128 , demyelination 129 , and superantigen activity 130 . Furthermore, the cytoplasmic accumulation of nucleic acids derived from activated TEs, including double-stranded RNA, reverse transcribed cDNA, or RNA–DNA hybrids, are increasingly regarded as potent immunological ‘adjuvants’ that may trigger autoimmune responses 131,132 and other toxicities when present in elevated quantities 133,134 .…”

An ancestral retroviral protein identified as a therapeutic target in type-1 diabetes

“…HERVs are remnants of viral infections of the primate germline millions of years ago, which have been transmitted to their progeny. Tens of HERV families have been described, representing 8% of the human genome -few of which have been associated with several autoimmune diseases such as systemic lupus erythematous, rheumatoid arthritis, MS, amyotrophic lateral sclerosis, and Sjögren's syndrome (13,24,(46)(47)(48). In particular, the HERV-W family has been involved in the pathogenesis of MS through its envelope protein HERV-W-Env, also known as MSRV-Env (23)(24)(25).…”

“…Despite decades of research, no causative link between viral infections and T1D pathogenesis has been confirmed (6). A new type of pathogenic element is emerging in the etiology of autoimmune diseases, the human endogenous retroviruses (HERVs), which are remnants of ancient viral infections that occurred millions of years ago (13). HERVs were generated by a process called endogenization, which happened when environmental retroviruses infected the germinal cells of hosts during evolution, leading to their transmission into Human endogenous retroviruses (HERVs), remnants of ancestral viral genomic insertions, are known to represent 8% of the human genome and are associated with several pathologies.…”

Human endogenous retroviruses and cancer

“…The resultant DNA is later integrated into host DNA through viral integrase enzyme. Viral-integrated DNA (proviral DNA) is translated and transcribed to proteins as part of host genome using the genetic machinery of infected cell 1-3 . …”