IFITMs Inhibit Cell Fusion Mediated by Trophoblast Syncytins

Type I interferon (IFN) induced by virus infections during pregnancy causes placental damage, though the mechanisms and identities of IFN-stimulated genes that are involved remain under investigation. The IFN-induced transmembrane proteins (IFITMs) inhibit virus infections by preventing virus membrane fusion with cells and by inhibiting fusion of infected cells (syncytialization). Fusion of placental trophoblasts via expression of endogenous retroviral fusogens known as Syncytins forms the syncytiotrophoblast, a multinucleated cell structure essential for fetal development. We found that IFN blocks fusion of BeWo human placental trophoblasts. Stably-expressed IFITMs 1, 2, and 3 also blocked fusion of these trophoblasts, while making them more resistant to virus infections. Conversely, stable knockdown of IFITMs in BeWo trophoblasts increased their spontaneous fusion and allowed fusion in the presence of IFN, while also making the cells more susceptible to virus infection. Overall, our data demonstrate that IFITMs are anti-viral and anti-fusogenic in trophoblasts.

The zinc finger protein REF-2 functions with the Hox genes to inhibit cell fusion in the ventral epidermis of C. elegans

During larval development in C. elegans, some of the cells of the ventral epidermis, the Pn.p cells, fuse with the growing epidermal syncytium hyp7. The pattern of these cell fusions is regulated in a complex, sexually dimorphic manner. It is essential that some Pn.p cells remain unfused in order for some sex-specific mating structures to be generated. The pattern of Pn.p cell fusion is regulated combinatorially by two genes of the C. elegans Hox gene cluster: lin-39 and mab-5. Some of the complexity in the Pn.p cell fusion pattern arises because these two Hox proteins can regulate each other’s activities. We describe a zinc-finger transcription factor, REF-2, that is required for the Pn.p cells to be generated and to remain unfused. REF-2 functions with the Hox proteins to prevent Pn.p cell fusion. ref-2 may also be a transcriptional target of the Hox proteins.