Placental endogenous retrovirus (ERV): structural, functional, and evolutionary significance

Abstract

That endogenous retrovirus (ERV) is present within the placenta of humans and other mammals has been known for the past 25 years, but the significance of this observation is still not fully understood. Much molecular biological data have emerged in recent years to support the earlier electron microscopic data on the presence of placental ERV. The evidence for ERV in animal and human placental tissue is presented, then integrated with data on the the presence of ERV in a range of other tissues, in particular teratocarcinoma cells. Placental invasiveness and maternal immunosuppression are then discussed in relation to metalloproteinase secretion, the immunosuppressive potential of retroviruses, and placental growth factors, while the evidence for a functional link between placental protooncogenes and trophoblast malignancy is reviewed. Finally, placental development, structure, and life span are discussed within an evolutionary context. The hypothesis that one or more ancient trophoblastic ERVs could have played a role in the evolution and divergence of all placental mammals is evaluated. Bio-

Endogenous retroviruses

“…They have also been identified in 10 out of 16 HERV elements containing complete env genes in the human genome, with only the putative 6 full-length Env proteins from the HERV-K(HML-2) family not harboring an ISD [60]. Immunosuppressive functions of animal and human endogenous retroviral Env proteins have essentially been implicated in two processes: induction of immune tolerance at the materno-fetal barrier via a physiological expression in the placenta [88] and suppression of an antitumoral immune response through aberrant expression in cancers. Somewhat reminiscent of the possibly context-dependent physiological and nonphysiological consequences of cell fusions mediated by Syncytin-1, the immunosuppressive effects of ERV Env proteins, which might possibly serve an important physiological goal by induction of fetomaternal tolerance, could have deleterious consequences when active in tumors.…”

An abundant placental transcript containing an IAP-LTR is allelic to mouse pregnancy-specific glycoprotein 23 (Psg23): cloning and genetic analysis

“…Placental transcription of endogenous retroviruses (ERVs) has been described in a wide variety of mammalian species (Harris, 1998). The function of such transcription is unclear and a variety of proposals implicate ERVs in suppression of maternal immune responses (Venables et al, 1995), trophoblast differentiation (Lin et al, 2000), trophoblastic cell syncytium formation (Mi et al, 2000) and implantation (Espinosa and Villarreal, 2000).…”

Conceptus implantation and placentation: molecules related to epithelial–mesenchymal transition, lymphocyte homing, endogenous retroviruses, and exosomes

“…Despite this prevalence in the mammalian genome, these were once considered non-functional junk DNAs. However, it is now realized that ERVs play biological roles in protection against retroviral infection [80] and in placental development [81,82]. Recently, it was found that high levels of transcripts found in ES cells, most of which are expressed in two-cell stage embryos, are induced by ERVs' LTRs, suggesting the possibility that the foreign sequences have helped to drive cell-fate regulation of early embryos in placental mammals [83].…”