Molecular mechanisms mediated by Human Endogenous Retroviruses (HERVs) in autoimmunity

Eight per cent of the human genome is derived from the integration of retroviral sequences that were incorporated in our DNA more than 25 million years ago. Although some of these elements show mutations and deletions, some HERVs are transcriptionally active and produce functional proteins. Different mechanisms have been described which link HERVs to some chronic diseases such as several cancers, nervous system diseases and autoimmune rheumatic and connective tissue diseases. They could cause disease because of their capacity for being moved and inserted next to certain genes whose expression would be consequentially altered. Another way in which disease could potentially arise is when HERV-encoded proteins are expressed. These proteins would be considered as 'foreign' and they could trigger B-cells to produce antibodies against them, which, in turn, might cross-react with other proteins of our bodies. This mechanism could give rise to autoimmune diseases such as rheumatoid arthritis (RA), lupus erythematosus, Sjogren's syndrome (SJS), mixed connective tissue diseases and inflammatory neurological disease. Furthermore, it should be pointed out that HERV-proteins may act as superantigens. Interestingly, some environmental agents seem to induce the expression of HERVs. Thus, ultraviolet light and several chemical agents could reactivate such sequences by altering their structure without modifying their nucleotide composition when the methylation pattern is changed. Therefore, the epigenetic changes observed in pathological conditions such as systemic lupus erythematosus (SLE) or cancer could be translated into an effect on the activation of some of the retro-elements present in our genome which ultimately could have a direct or indirect role on the initiation and clinical evolution of certain chronic diseases. Copyright (C) 2009 John Wiley & Sons, Ltd.