186 Immunosuppressive human endogenous retrovirus K (HERV-K) is expressed in human villous and extravillous cytotrophoblasts

Abstract

Overexpression of different human endogenous retroviruses (HERVs) has been shown in stem cell tumors, melanomas, human embryonic stem cells as well as in the placenta. The envelope proteins of HERV-W (also known as syncytin 1) and HERV-FRD (syncytin 2) were shown to be involved in cell fusion allowing to generate the syncytiotrophoblast in the human placenta. One of them, syncytin 2, was shown to be immunosuppressive, the immunosuppressive activity was associated with its immunosuppressive (isu) domain. Here we report the expression of another HERV, HERV-K, which is characterised by open reading frames for all viral genes. Using real time PCR, immunohistochemistry and Western blot analysis, expression of HERV-K was studied in normal placental tissue of different gestational ages. The transmembrane envelope (TM) protein of HERV-K was found exclusively in villous and extravillous trophoblast cells, sparing syncytiotrophoblast and other cells. The expression increased up to the second trimester and later decreased. This is the first report showing expression of the TM protein of HERV-K in normal human placental tissue with an exclusive expression in the trophoblast, suggesting a potential involvement of HERV-K in placentogenesis and pregnancy. In parallel the immunosuppressive properties of the TM protein and the corresponding isu peptide were demonstrated. Therefore expression of the immunosuppressive TM protein of HERV-K may contribute to the protection of the human embryo.