Identification of the hASCT2-binding domain of the Env ERVWE1/syncytin-1 fusogenic glycoprotein

The cellular HERV-W envelope/syncytin-1 protein, encoded by the envelope gene of the ERVWE1 proviral locus is a fusogenic glycoprotein probably involved in the formation of the placental syncytiotrophoblast layer. Syncytin-1-induced in vitro cell-cell fusion is dependent on the interaction with hASCT2. As no receptor binding domain has been clearly defined in the SU of neither the HERV-W Env nor the retroviruses of the same interference group, we designed an in vitro binding assay to evaluate the interaction of the HERV-W envelope with the hASCT2 receptor. Using truncated HERV-W SU subunits, a region consisting of the N-terminal 124 amino acids of the mature SU glycoprotein was determined as the minimal receptor-binding domain. This domain contains several sub-domains which are poorly conserved among retroviruses of this interference group but a region of 18 residus containing the SDGGGX(2)DX(2)R conserved motif was proved to be essential for syncytin-1-hASCT2 interaction

AMP, filiation... et demain ? Pistes de réflexion

International audienceSans partager la même lecture, deux universitaires, Aline Cheynet de Beaupré et Valérie Depadt, réfléchissent aux difficultés liées à la situation actuelle du droit de la filiation au lendemain de la loi de bioéthique du 2 août 2021 (1) . Celle-ci semble avoir marqué un tournant important mais en contenant un certain nombre de dispositions délicates à intégrer dans le droit positif. L'identification des problématiques puis leur analyse devraient permettre de relever quelques difficultés éventuelles dans l'application du texte. Ce bilan rejoint l'esprit d'un audit sans prétendre proposer des solutions, lesquelles relèvent plutôt de politique législative

AMP, filiation... et demain ? Pistes de réflexion

International audienceSans partager la même lecture, deux universitaires, Aline Cheynet de Beaupré et Valérie Depadt, réfléchissent aux difficultés liées à la situation actuelle du droit de la filiation au lendemain de la loi de bioéthique du 2 août 2021 (1) . Celle-ci semble avoir marqué un tournant important mais en contenant un certain nombre de dispositions délicates à intégrer dans le droit positif. L'identification des problématiques puis leur analyse devraient permettre de relever quelques difficultés éventuelles dans l'application du texte. Ce bilan rejoint l'esprit d'un audit sans prétendre proposer des solutions, lesquelles relèvent plutôt de politique législative

AMP, filiation... et demain ? Pistes de réflexion

International audienceSans partager la même lecture, deux universitaires, Aline Cheynet de Beaupré et Valérie Depadt, réfléchissent aux difficultés liées à la situation actuelle du droit de la filiation au lendemain de la loi de bioéthique du 2 août 2021 (1) . Celle-ci semble avoir marqué un tournant important mais en contenant un certain nombre de dispositions délicates à intégrer dans le droit positif. L'identification des problématiques puis leur analyse devraient permettre de relever quelques difficultés éventuelles dans l'application du texte. Ce bilan rejoint l'esprit d'un audit sans prétendre proposer des solutions, lesquelles relèvent plutôt de politique législative

Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer

International audienceThe prostate-specific antigen (PSA) is the main diagnostic biomarker for prostate cancer in clinical use, but it lacks specificity and sensitivity, particularly in low dosage values 1. 'How to use PSA' remains a current issue, either for diagnosis as a gray zone corresponding to a concentration in serum of 2.5-10 ng/ml which does not allow a clear differentiation to be made between cancer and noncancer 2 or for patient follow-up as analysis of post-operative PSA kinetic parameters can pose considerable challenges for their practical application 3,4. Alternatively, noncoding RNAs (ncRNAs) are emerging as key molecules in human cancer, with the potential to serve as novel markers of disease, e.g. PCA3 in prostate cancer 5,6 and to reveal uncharacterized aspects of tumor biology. Moreover, data from the ENCODE project published in 2012 showed that different RNA types cover about 62% of the genome. It also appears that the amount of transcriptional regulatory motifs is at least 4.5x higher than the one corresponding to protein-coding exons. Thus, long terminal repeats (LTRs) of human endogenous retroviruses (HERVs) constitute a wide range of putative/candidate transcriptional regulatory sequences, as it is their primary function in infectious retroviruses. HERVs, which are spread throughout the human genome, originate from ancestral and independent infections within the germ line, followed by copy-paste propagation processes and leading to multicopy families occupying 8% of the human genome (note that exons span 2% of our genome). Some HERV loci still express proteins that have been associated with several pathologies including cancer 7-10. We have designed a high-density microarray, in Affymetrix format, aiming to optimally characterize individual HERV loci expression, in order to better understand whether they can be active, if they drive ncRNA transcription or modulate coding gene expression. This tool has been applied in the prostate cancer field (Figure 1)

Direct Involvement of HERV-W Env Glycoprotein in Human Trophoblast Cell Fusion and Differentiation

We recently demonstrated that the product of the HERV-W env gene, a retroviral envelope protein also dubbed syncytin, is a highly fusogenic membrane glycoprotein inducing the formation of syncytia on interaction with the type D mammalian retrovirus receptor. In addition, the detection of HERV-W Env protein (Env-W) expression in placental tissue sections led us to propose a role for this fusogenic glycoprotein in placenta formation. To evaluate this hypothesis, we analyzed the involvement of Env-W in the differentiation of primary cultures of human villous cytotrophoblasts that spontaneously differentiate by cell fusion into syncytiotrophoblasts in vitro. First, we observed that HERV-W env mRNA and glycoprotein expression are colinear with primary cytotrophoblast differentiation and with expression of human chorionic gonadotropin (hCG), a marker of syncytiotrophoblast formation. Second, we observed that in vitro stimulation of trophoblast cell fusion and differentiation by cyclic AMP is also associated with a concomitant increase in HERV-W env and hCG mRNA and protein expression. Finally, by using specific antisense oligonucleotides, we demonstrated that inhibition of Env-W protein expression leads to a decrease of trophoblast fusion and differentiation, with the secretion of hCG in culture medium of antisense oligonucleotide-treated cells being decreased by fivefold. Taken together, these results strongly support a direct role for Env-W in human trophoblast cell fusion and differentiation