Syncytin-A and syncytin-B, two fusogenic placenta-specific murine envelope genes of retroviral origin conserved in Muridae
Syncytin-A and syncytin-B, two fusogenic placenta-specific murine envelope genes of retroviral origin conserved in Muridae
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DOI：
10.1073/pnas.0406509102
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发表时间：
2005-01-18
影响因子：
11.1
通讯作者：
Heidmann, T
中科院分区：
文献类型：
--
作者：
Dupressoir, A;Marceau, G;Heidmann, T
最近，我们和其他人已经确定了两种人类内源性逆转录病毒，它们在2500万至4000万年前进入灵长类动物谱系，编码高度融合的逆转录病毒包膜蛋白（合胞素-1和-2），可能参与胎盘合胞体滋养层的形成，滋养层细胞在母胎界面融合。目前，在小鼠基因组数据库中进行的系统性计算机检索鉴定出两种完全编码的包膜基因，其以独特的拷贝存在并且与任何已知的鼠内源性逆转录病毒无关，我们将其命名为合胞素-A和-B。定量RT-PCR表明胎盘特异性表达的两个基因，随着增加的转录水平在这个器官从9.5至14.5天postcoplant。胎盘冰冻切片的原位杂交进一步定位这些转录本在含合胞体滋养层的胎盘中。一致地，我们表明，这两个基因可以触发细胞-细胞融合在离体转染试验中，不同的细胞类型特异性表明不同的受体的使用。在所有测试的鼠科动物（小鼠、大鼠、沙鼠、田鼠和仓鼠）中发现了与合胞素A和合胞素B直向同源的基因，并揭示了它们的编码状态的惊人保守性，将它们进入啮齿动物谱系的时间定在大约2000万年前。总之，这些数据有力地证明了合胞素-A和-B在小鼠合胞滋养层形成中的关键作用，从而揭示了一种相当独特的情况，即两对内源性逆转录病毒，独立获得的灵长类动物和啮齿类动物谱系，将被积极选择为收敛的生理作用。
Recently, we and others have identified two human endogenous retroviruses that entered the primate lineage 25-40 million years ago and that encode highly fusogenic retroviral envelope proteins (syncytin-1 and -2), possibly involved in the formation of the placenta syncytiotrophoblast layer generated by trophoblast cell fusion at the materno-fetal interface. A systematic in silico search throughout mouse genome databases presently identifies two fully coding envelope genes, present as unique copies and unrelated to any known murine endogenous retrovirus, that we named syncytin-A and -B. Quantitative RT-PCR demonstrates placenta-specific expression for both genes, with increasing transcript levels in this organ from 9.5 to 14.5 days postcoitum. In situ hybridization of placenta cryosections further localizes these transcripts in the syncytiotrophoblast-containing labyrinthine zona. Consistently, we show that both genes can trigger cell-cell fusion in ex vivo transfection assays, with distinct cell type specificities suggesting different receptor usage. Genes orthologous to syncytin-A and -B and disclosing a striking conservation of their coding status are found in all Muridae tested (mouse, rat, gerbil, vole, and hamster), dating their entry into the rodent lineage approximate to 20 million years ago. Together, these data strongly argue for a critical role of syncytin-A and -B in murine syncytiotrophoblast formation, thus unraveling a rather unique situation where two pairs of endogenous retroviruses, independently acquired by the primate and rodent lineages, would have been positively selected for a convergent physiological role.