Mallet François, Prudhomme Sarah
UMR 2714 CNRS-bioMérieux, IFR128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon cedex 07, France.
J Soc Biol. 2004;198(4):399-412.
The data provided by the sequencing of the human genome showed that retroviral-like elements constituted approximately 8 % of the euchromatin. The origin of these elements, their propagation leading to an organization in families, their genetic structure and the identification of the fonctional domains of the components of these elements are described. Placenta is used as a model to illustrate the physiological involvement of HERVs. Transcriptional regulatory element (LTR) functions and the putative implication of retroviral proteins in resistance to infection, immunosuppression, and cellular differentiation are clarified. The data implicating the envelope encoded by the ERVWE1 locus of the HERV-W family in the fusion process, leading to syncytiotrophoblast formation, is analysed. The putative pathological effect of HERVs is illustrated by the expression of the HERV-K superfamily in cancer. More precisely, the association between the Rec regulatory protein encoded by HERV-K(HML-2) and testicular tumorigenesis is developed. Whether HERVs are triggers or markers in other physiopathological contexts is discussed. To conclude, the dual benefit-hazard underlying the acquisition/propagation of HERVs is examined with respect to species evolution, considering the multicopy trait of HERV families and the mainly multi-factorial aspect of autoimmune diseases and cancers.
人类基因组测序提供的数据表明，类逆转录病毒元件约占常染色质的8%。本文描述了这些元件的起源、它们通过繁殖形成家族组织的过程、它们的遗传结构以及这些元件组成部分功能域的鉴定。以胎盘作为模型来说明内源性逆转录病毒（HERVs）的生理作用。阐明了转录调控元件（长末端重复序列，LTR）的功能以及逆转录病毒蛋白在抗感染、免疫抑制和细胞分化中的潜在作用。分析了HERV-W家族的ERVWE1基因座编码的包膜蛋白在融合过程中导致合体滋养层形成的数据。HERV-K超家族在癌症中的表达说明了HERVs的潜在病理作用。更确切地说，详细阐述了HERV-K（HML-2）编码的Rec调控蛋白与睾丸肿瘤发生之间的关联。讨论了HERVs在其他生理病理情况下是触发因素还是标志物。最后，考虑到HERV家族的多拷贝特性以及自身免疫性疾病和癌症主要的多因素特点，从物种进化的角度探讨了HERVs获得/传播所带来的双重利弊。
