Identification of an endogenous retroviral envelope gene with fusogenic activity and placenta-specific expression in the rabbit: a new "syncytin" in a third order of mammals.
Identification of an endogenous retroviral envelope gene with fusogenic activity and placenta-specific expression in the rabbit: a new "syncytin" in a third order of mammals.
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DOI：
10.1186/1742-4690-6-107
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发表时间：
2009-11-27
期刊：
影响因子：
3.3
通讯作者：
Heidmann T
中科院分区：
文献类型：
--
作者：
Heidmann O;Vernochet C;Dupressoir A;Heidmann T
合胞素是一种源于逆转录病毒的包膜基因，在胎盘形成过程中被宿主吸收并介导了一种特殊的功能。其中两个基因已经在灵长类动物中被发现，在啮齿类动物中也发现了两个不同的非同源基因。在这里，我们发现了兔兔（Oryctolagus cuniculus）（属于lagomorpha目）的一个逆转录病毒起源的包膜（env）基因，它具有真正的合胞蛋白的特征，我们将其命名为syncytin- ory1。利用不间断开放阅读框在兔基因组中对全长env基因进行了计算机搜索，首先确定了两个候选基因，并通过从大量组织中分离的RNA的定量RT-PCR检测了它们在胎盘中的特异性表达。这导致鉴定出胎盘特异性表达的env基因，属于兔基因组中有限拷贝数的内源性逆转录因子家族。在cmv驱动的表达载体和瞬时转染实验中克隆胎盘表达的env基因后，功能表征表明在体外细胞-细胞融合实验中具有融合活性和假型的传染性。兔合胞素- ory1的受体被发现与人合胞素-1的受体相同，即先前鉴定的ASCT2转运体。用ASCT2表达载体转导的仓鼠A23细胞和用syncytin-Ory1转导的A23细胞之间的共培养融合实验证实了这一点。最后，用syncyin - ory1探针对兔胎盘切片进行原位杂交，发现在胎盘叶和母体蜕膜之间的交界区有特异性表达，侵入的合胞胎儿组织与母体蜕膜接触形成迷宫，这与合胞滋养细胞形成的作用一致。合胞素- ory1基因在狐猴科中发现，但在狐猴科中没有发现，因此应该在1200万至3000万年前进入狐猴目。在胎盘形成过程中，在第三目哺乳动物中发现了一种新的合胞素基因，这有力地支持了这样一种观点，即在一些情况下，逆转录病毒感染导致了基因的独立捕获，这些基因被积极地选择为趋同的生理作用。
Syncytins are envelope genes of retroviral origin that have been co-opted by the host to mediate a specialized function in placentation. Two of these genes have already been identified in primates, as well as two distinct, non orthologous genes in rodents. Here we identified within the rabbit Oryctolagus cuniculus-which belongs to the lagomorpha order- an envelope (env) gene of retroviral origin with the characteristic features of a bona fide syncytin, that we named syncytin-Ory1. An in silico search for full-length env genes with an uninterrupted open reading frame within the rabbit genome first identified two candidate genes that were tested for their specific expression in the placenta by quantitative RT-PCR of RNA isolated from a large set of tissues. This resulted in the identification of an env gene with placenta-specific expression and belonging to a family of endogenous retroelements present at a limited copy number in the rabbit genome. Functional characterization of the identified placenta-expressed env gene after cloning in a CMV-driven expression vector and transient transfection experiments, demonstrated both fusogenic activity in an ex vivo cell-cell fusion assay and infectivity of pseudotypes. The receptor for the rabbit syncytin-Ory1 was found to be the same as that for human syncytin-1, i.e. the previously identified ASCT2 transporter. This was demonstrated by a co-culture fusion assay between hamster A23 cells transduced with an expression vector for ASCT2 and A23 cells transduced with syncytin-Ory1. Finally, in situ hybridization of rabbit placenta sections with a syncytin-Ory1 probe revealed specific expression at the level of the junctional zone between the placental lobe and the maternal decidua, where the invading syncytial fetal tissue contacts the maternal decidua to form the labyrinth, consistent with a role in the formation of the syncytiotrophoblast. The syncytin-Ory1 gene is found in Leporidae but not in Ochotonidae, and should therefore have entered the lagomorpha order 12-30 million years ago. The identification of a novel syncytin gene within a third order of mammals displaying syncytiotrophoblast formation during placentation strongly supports the notion that on several occasions retroviral infections have resulted in the independent capture of genes that have been positively selected for a convergent physiological role.
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影响因子：
3.3
作者：
Blaise, S;de Parseval, N;Heidmann, T
通讯作者：
Heidmann, T
影响因子：
5.4
作者：
Blaise, S;Ruggieri, A;Heidmann, T
通讯作者：
Heidmann, T
DOI：
10.1073/pnas.0305763101
发表时间：
2004-02-10
影响因子：
11.1
作者：
Mallet, F;Bouton, O;Mandrand, B
通讯作者：
Mandrand, B
DOI：
10.1073/pnas.0707873105
发表时间：
2007-12-18
影响因子：
11.1
作者：
Mangeney, Marianne;Renard, Martial;Heidmann, Thierry
通讯作者：
Heidmann, Thierry
DOI：
10.1073/pnas.0902925106
发表时间：
2009-07-21
影响因子：
11.1
作者：
Dupressoir, Anne;Vernochet, Cecile;Heidmann, Thierry
通讯作者：
Heidmann, Thierry