Dewannieux Marie, Ribet David, Heidmann Thierry
Unité des Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs, CNRS UMR 8122, Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94805 Villejuif, France.
Biologicals. 2010 May;38(3):366-70. doi: 10.1016/j.biologicals.2010.01.006. Epub 2010 Mar 23.
Mammalian genomes contain a heavy load of retroelements, which are mobile sequences requiring reverse transcription for their amplification. A significant proportion of these elements is of retroviral origin, with thousands of sequences resembling the integrated form of infectious retroviruses with two LTRs bordering internal regions homologous to the gag, pol, and env genes. These elements, named endogenous retroviruses (ERVs), are thought to be the remnants of ancestral germline infections by active retroviruses, which have thereafter been transmitted in a Mendelian manner. The sequencing of several mammalian genomes has allowed a comprehensive study of their ERVs. They can be grouped according to sequence homologies into 10-100 families per genome, each containing a few to several hundred elements. Strong similarities between ERVs and present-day retroviruses can be inferred from phylogenetic analyses performed on the pol or env genes, suggesting a common history. As a general rule, most ERVs are old and degenerated, with their open reading frames disrupted, but a few proviruses have retained intact genes and the corresponding proteins can thus be expressed. Some elements still contain gag and pol genes that drive the synthesis of viral particles, as well as envelope genes whose product can be incorporated on their cognate or heterologous viral particles. This presentation will review the general properties of endogenous retroviruses, in relation with their possible consequences on vaccine production.
哺乳动物基因组中含有大量逆转录元件,这些元件是需要通过逆转录进行扩增的可移动序列。这些元件中有很大一部分起源于逆转录病毒,数以千计的序列类似于具有两个长末端重复序列(LTR)的传染性逆转录病毒的整合形式,两个LTR界定了与gag、pol和env基因同源的内部区域。这些元件被称为内源性逆转录病毒(ERV),被认为是活跃逆转录病毒对祖先种系感染的残余物,此后以孟德尔方式进行传播。对几个哺乳动物基因组的测序使得对其ERV进行全面研究成为可能。它们可以根据序列同源性分为每个基因组10 - 100个家族,每个家族包含几个到几百个元件。通过对pol或env基因进行系统发育分析,可以推断出ERV与当今逆转录病毒之间存在很强的相似性,这表明它们有共同的历史。一般来说,大多数ERV很古老且已退化,其开放阅读框被破坏,但少数前病毒保留了完整的基因,因此相应的蛋白质可以表达。一些元件仍然含有驱动病毒颗粒合成的gag和pol基因,以及其产物可以整合到同源或异源病毒颗粒上的包膜基因。本报告将回顾内源性逆转录病毒的一般特性,以及它们对疫苗生产可能产生的影响。