Regulation of the expression of Human Endogenous Retrovirus envelope genes and analysis of their function

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The human genome harbours sequences, which originate from viruses known as retroviruses. It has been estimated that about 8% of human DNA is composed of these retroviral sequences. These sequences have been integrated in the genome of primates 25 million years ago. Although most of these DNA regions are no longer capable of producing viruses, some have been reported to have retained the capacity to generate viruses, which, although non-infectious, can be observed in the extracellular milieu. These viruses are termed Human Endogenous Retroviruses (HERV). The presence of HERVs in the human organism has been rarely associated with biological phenomena, although four HERV proteins termed Syncytin-1, Syncytin-2, EnvV2 and EnvP(b) representing the envelope proteins of ancient retroviruses could be important for the development of the placenta. Based on our previous results, we are interested in testing their involvement in placenta development through the study of the mechanism of regulation of their expression in trophoblasts (placenta-derived cells), their localisation inside the cell and by analysing their impact on differentiation of these cells and immunosuppression linked to the placenta. Several tools (including specific antibodies, new chimeric proteins and RNA interference-based RNA molecules) will be used in this study to understand the implication of these retrovirus-related proteins in the various roles that are attributed to trophoblasts. These experiments will shed light on the mechanism of action and the mode of regulation of expression of these genes with relation ot the placenta and are therefore part of a fundamental research program. These results will bring a new light on how these HERV genes are turned on in trophoblasts and how they affect important biological processes and functions associated to the placenta.