| First Author | Buchrieser J | Year | 2019 |
| Journal | Science | Volume | 365 |
| Issue | 6449 | Pages | 176-180 |
| PubMed ID | 31296770 | Mgi Jnum | J:323383 |
| Mgi Id | MGI:6333017 | Doi | 10.1126/science.aaw7733 |
| Citation | Buchrieser J, et al. (2019) IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise. Science 365(6449):176-180 |
| abstractText | Elevated levels of type I interferon (IFN) during pregnancy are associated with intrauterine growth retardation, preterm birth, and fetal demise through mechanisms that are not well understood. A critical step of placental development is the fusion of trophoblast cells into a multinucleated syncytiotrophoblast (ST) layer. Fusion is mediated by syncytins, proteins deriving from ancestral endogenous retroviral envelopes. Using cultures of human trophoblasts or mouse cells, we show that IFN-induced transmembrane proteins (IFITMs), a family of restriction factors blocking the entry step of many viruses, impair ST formation and inhibit syncytin-mediated fusion. Moreover, the IFN inducer polyinosinic:polycytidylic acid promotes fetal resorption and placental abnormalities in wild-type but not in Ifitm-deleted mice. Thus, excessive levels of IFITMs may mediate the pregnancy complications observed during congenital infections and other IFN-induced pathologies. |
