Abstract
Numerous copies of endogenous retroviruses are present in the genome of mammals including man. Although most of them are defective, some, e.g., the human endogenous retroviruses HERV-K, were found to be expressed under certain physiological conditions. For instance, HERV-K is expressed in germ cell tumours and melanomas as well as in the placenta. Most exogenous retroviruses including the human immunodeficiency virus HIV-1 induce severe immunodeficiencies and there is increasing evidence that the transmembrane envelope (TM) proteins of these retroviruses may be involved. We show here that HERV-K particles released from a human teratocarcinoma cell line, a recombinant TM protein and a peptide corresponding to a highly conserved so-called immunosuppressive domain in the TM protein of HERV-K inhibit the proliferation of human immune cells, induce modulation of the expression of numerous cytokines, and modulate the expression of cellular genes as detected by a microarray analysis. The changes in cytokine release and gene expression induced by the TM protein of HERV-K are similar to those found previously induced by the TM protein of HIV-1. These data suggest that the mechanism of immunosuppression may be similar for different retroviruses and that the expression of the TM protein in tumours and in the placenta may suppress immune responses and thus prevent rejection of the tumour and the embryo.
Highlights
In the last years the expression of human endogenous retroviruses (HERV) in tumours and physiologically healthy tissues was intensively studied [1,2,3]
Inactivated retrovirus preparations, their transmembrane envelope (TM) proteins and synthetic peptides corresponding to the isu domain of their TM proteins were found to inhibit proliferation of peripheral blood mononuclear cells (PBMCs) and to modulate the cytokine release and gene expression
We and others had shown that particles of HIV-1 [27,35], of porcine endogenous retrovirus (PERV)-A, PERV-B and the murine leukaemia virus (MuLV) [36], of FeLV [37,38], of the baboon endogenous retrovirus (BaEV), and of a deltaretrovirus [39,40] as well as of the Koala retrovirus (KoRV) [41] were able to inhibit lymphocyte activation and modulated IL10 release in treated immune cells
Summary
In the last years the expression of human endogenous retroviruses (HERV) in tumours and physiologically healthy tissues was intensively studied [1,2,3]. HERV-K is one of the few human endogenous retroviruses with intact open reading frames for all viral proteins [4,5]. Non-infectious virus-like particles and viral proteins have been found in human germ line tumours [6,7,8] and melanomas [9,10,11]. Genes of other human endogenous retroviruses such as syncytin 1 (the envelope protein of HERV-W) [13,14,15] and syncytin 2 (the envelope protein of HERV-FRD) [16,17] were found to be expressed in the placenta. It is important to note that these endogenous retroviruses are not related and that each mammalian species utilises (‘‘enslaved’’) a different endogenous retrovirus
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