Human Endogenous Retroviruses as Contributors of Exosomemediated Autoimmunity in Systemic Lupus Erythematosus


Haya AbuZuluf

Volume 3
Fall 2017 / Winter 2018

SUMMARY At least 8% of the human genome was formed by integration of retroviral DNA sequences. These sequences are remnants of ancient infections that have accumulated mutations over millions of years. Although human endogenous retroviruses (HERVs) were previously thought to be inactive, they are now emerging as potential contributors of autoimmune diseases. Environmental and epigenetic factors have been shown to activate the expression of HERVs in pathological conditions such as Systemic Lupus Erythematosus (SLE). SLE is a poorly understood non-organ specific autoimmune isease lacking diagnostic criteria and curative treatments. It has been suggested that an unfortunate interplay of genetic susceptibility and environmental factors play an important role in generating an abnormal autoimmune response in SLE patients. HERVs have been proposed to be the bridge linking environmental factors to the pathogenesis of SLE. However, no clear mechanisms of causation have been identified in this association. This review outlines the key HERVs implicated in SLE, the factors that influence their activation and the proposed mechanisms utilized by HERVs in the etiopathogenesis of SLE. In addition, Investigate the potential of exosomes in playing a role in HERV-mediated stimulation of the immune system that in turn may contribute to activation and progression of SLE. The characterization of exosomal cargo will allow the identification of HERV products or sequences that may be transmitting intercellular signals involved in the immune dysregulation of SLE. Elucidating this association between HERVs and SLE may facilitate the development of novel diagnostic and therapeutic tools to combat this debilitating multi-system disease.