Resolving the confusion over the two specific cellular receptors for Syncytin-1 and other endogenous retroviruses

0580682 - ÚMG 2024 RIV CZ eng A - Abstrakt
Štafl, Kryštof - Trávníček, Martin - Hejnar, Jiří - Trejbalová, Kateřina
Resolving the confusion over the two specific cellular receptors for Syncytin-1 and other endogenous retroviruses.
Czech Chemical Society Symposium Series. Roč. 21, č. 5 (2023), č. článku L-29. ISSN 2336-7202.
[Annual meeting of the National Institute of Virology and Bacteriology (NIVB) /2./. 02.10.2023-05.10.2023, Kutná Hora]
Grant CEP: GA MŠMT(CZ) LX22NPO5103
Institucionální podpora: RVO:68378050
Klíčová slova: Syncytin-1 * cellular receptor * endogenous retroviruses
Obor OECD: Biochemistry and molecular biology
http://ccsss.cz/index.php/ccsss/issue/view/41

syncytin-1 is a human protein-coding gene of retroviral origin. During human placenta morphogenesis, the interaction of Syncytin-1 with the transmembrane protein ASCT2 (Alanine, Serine, Cysteine Transporter 2) triggers cell-to-cell fusion of trophoblasts, resulting in the formation of a syncytiotrophoblast, a large multinucleated syncytium1,2. The syncytiotrophoblast is the outermost surface of the human placenta. It facilitates the transport of nutrients and waste products across the maternal-fetal interface, produces hormones and cytokines, and protects the fetus from pathogens and the mother’s immune system. Altered behavior of Syncytin-1 may contribute to human placenta pathologies, including preeclampsia, low platelet syndrome/intrauterine growth restriction, and gestational trophoblastic diseases, e.g., mole and choriocarcinoma3.ASCT1, a sodium-dependent neutral amino acid transporter with a related structure to ASCT2, was postulated as an alternative Syncytin-1 cellular receptor1,4. Furthermore, both ASCT1 and ASCT2 have been reported to be receptors for the largest interference group, the RD114-and D-type (RDR) retroviruses. The contribution of both receptors to Syncytin-1-induced cell-cell fusion, as well as the receptor preference of RDR retroviruses, remain to be understood. In this study, we investigated the individual involvement of each receptor in the interaction with Syncytin-1 using three quantitative molecular assays (Fig. 1). We measured theinfection with the Syncytin-1-pseudotyped virus triggered by the ASCT2 or ASCT1 receptors independently. Further, we assessed the binding of Syncytin-1 to ASCT2 vs. ASCT1 on the cell surface. Finally, we determined the Syncytin-1 fusogenic activity induced by the interaction with ASCT2 or ASCT1.Our results demonstrate that ASCT1 is at least two orders of magnitude less active as a receptor than ASCT2, which casts doubt on the importance of ASCT1 for syncytiotrophoblast differentiation.Interestingly, certain members of the RDR group are able to use both receptors efficiently. These findings demonstrate the variability of the interaction between homologous envelope glycoproteins and a particular receptor molecule.Our results highlight the function of ASCT2 during placental development and challenge the physiological role of ASCT1 during Syncytin-1-induced fusion.
Trvalý link: https://hdl.handle.net/11104/0349443