A paradigm for virus-host coevolution: sequential counter-adaptations between endogenous and exogenous retroviruses.
A paradigm for virus-host coevolution: sequential counter-adaptations between endogenous and exogenous retroviruses.
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DOI：
10.1371/journal.ppat.0030170
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发表时间：
2007-11
期刊：
影响因子：
6.7
通讯作者：
Palmarini M
中科院分区：
文献类型：
--
作者：
Arnaud F;Caporale M;Varela M;Biek R;Chessa B;Alberti A;Golder M;Mura M;Zhang YP;Yu L;Pereira F;Demartini JC;Leymaster K;Spencer TE;Palmarini M
内源性逆转录病毒（ERV）是古老的逆转录病毒感染的宿主生殖系垂直传播的一代又一代的残余。据推测，一些ERV被宿主用作限制因子来阻断致病性逆转录病毒的感染。事实上，一些ERV有效地干扰相关外源性逆转录病毒的复制。然而，数据表明，这些机制已经影响了内源性和/或外源性逆转录病毒及其宿主的共同进化已经更难获得。绵羊是研究逆转录病毒-宿主协同进化的有趣模型系统，因为在这种动物物种中共存两种外源性（即，水平传播的）致癌逆转录病毒、Jaagsiekte绵羊逆转录病毒和地方性鼻肿瘤病毒，以及高度相关和生物活性的内源性逆转录病毒（enJSRVs）。在这里，我们分离并表征了27个enJSRV前病毒的进化历史和分子病毒学。在过去的500 - 700万年里，enJSRVs已经整合到宿主基因组中。两个enJSRV前病毒（enJS 56 A1和enJSRV-20），进入宿主基因组内的最后3百万年（之前和在物种形成的绵羊属内），收购在两个时间上不同的事件缺陷Gag多聚蛋白，导致一个转显性表型，能够阻止相关的外源性逆转录病毒的后期复制步骤。两种转显性原病毒在绵羊驯化之前或前后（19000年前）就固定在宿主基因组中。有趣的是，最近出现了一种逃避反显性enJSRVs的前病毒，很可能是在过去的200年里。因此，我们确定了顺序不同的事件在进化过程中，内源性和外源性逆转录病毒之间的进化拮抗作用的指示。这项研究有力地表明，内源化和选择ERVs作为限制因子是宿主对抗逆转录病毒感染的一种机制。所有脊椎动物的基因组都被“内源性”逆转录病毒（ERV）大量定殖。ERV来源于进化过程中宿主生殖细胞的逆转录病毒感染，导致病毒基因组永久整合到宿主DNA中。由于ERV整合在宿主基因组中，它们像任何其他宿主基因一样传递给后代。内源性逆转录病毒的功能尚不完全清楚，但一些ERV可以阻断水平传播的“外源性”致病性逆转录病毒的复制周期。这些观察结果导致的假设，ERVs保护主机在进化过程中对传入的致病性逆转录病毒。在这里，通过描述一组特定的内源性β逆转录病毒的绵羊（enJSRVs）的进化历史和分子病毒学，我们展示了一系列迷人的事件，揭示了宿主和逆转录病毒之间无休止的斗争。特别是，我们发现：（i）在绵羊属内物种形成之前进入宿主基因组的两个enJSRV基因座（1300万年前）获得，整合后，突变的缺陷病毒蛋白能够阻断外源相关的逆转录病毒;（ii）这两个转显性enJSRV基因座成为固定在宿主基因组之前或前后羊驯化（10，000年前）;（iii）JSRV/enJSRVs组的ERV对绵羊基因组的入侵仍在进行中;和（iv）最近出现了新的病毒（不到200年前），其可以逃避反显性enJSRV基因座。这项研究有力地表明，内源化和选择ERVs作为限制因子是宿主对抗逆转录病毒感染的一种机制。
Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections of the host germline transmitted vertically from generation to generation. It is hypothesized that some ERVs are used by the host as restriction factors to block the infection of pathogenic retroviruses. Indeed, some ERVs efficiently interfere with the replication of related exogenous retroviruses. However, data suggesting that these mechanisms have influenced the coevolution of endogenous and/or exogenous retroviruses and their hosts have been more difficult to obtain. Sheep are an interesting model system to study retrovirus-host coevolution because of the coexistence in this animal species of two exogenous (i.e., horizontally transmitted) oncogenic retroviruses, Jaagsiekte sheep retrovirus and Enzootic nasal tumor virus, with highly related and biologically active endogenous retroviruses (enJSRVs). Here, we isolated and characterized the evolutionary history and molecular virology of 27 enJSRV proviruses. enJSRVs have been integrating in the host genome for the last 5–7 million y. Two enJSRV proviruses (enJS56A1 and enJSRV-20), which entered the host genome within the last 3 million y (before and during speciation within the genus Ovis), acquired in two temporally distinct events a defective Gag polyprotein resulting in a transdominant phenotype able to block late replication steps of related exogenous retroviruses. Both transdominant proviruses became fixed in the host genome before or around sheep domestication (∼ 9,000 y ago). Interestingly, a provirus escaping the transdominant enJSRVs has emerged very recently, most likely within the last 200 y. Thus, we determined sequentially distinct events during evolution that are indicative of an evolutionary antagonism between endogenous and exogenous retroviruses. This study strongly suggests that endogenization and selection of ERVs acting as restriction factors is a mechanism used by the host to fight retroviral infections. The genome of all vertebrates is heavily colonized by “endogenous” retroviruses (ERVs). ERVs derive from retrovirus infections of the germ cells of the host during evolution, leading to permanent integration of the viral genome into the host DNA. Because ERVs are integrated in the host genome, they are transmitted to subsequent generations like any other host gene. The function of endogenous retroviruses is not completely clear, but some ERVs can block the replication cycle of horizontally transmitted “exogenous” pathogenic retroviruses. These observations lead to the hypothesis that ERVs have protected the host during evolution against incoming pathogenic retroviruses. Here, by characterizing the evolutionary history and molecular virology of a particular group of endogenous betaretroviruses of sheep (enJSRVs) we show a fascinating series of events unveiling the endless struggle between host and retroviruses. In particular, we discovered that: (i) two enJSRV loci that entered the host genome before speciation within the genus Ovis (∼ 3 million y ago) acquired, after their integration, a mutated defective viral protein capable of blocking exogenous related retroviruses; (ii) both these transdominant enJSRV loci became fixed in the host genome before or around sheep domestication (∼ 10,000 y ago); (iii) the invasion of the sheep genome by ERVs of the JSRV/enJSRVs group is still in progress; and (iv) new viruses have recently emerged (less than 200 y ago) that can escape the transdominant enJSRV loci. This study strongly suggests that endogenization and selection of ERVs acting as restriction factors is a mechanism used by the host to fight retroviral infections.
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影响因子：
30.8
作者：
Hughes, JF;Coffin, JM
通讯作者：
Coffin, JM
影响因子：
64.8
作者：
Best, S;LeTissier, P;Stoye, JP
通讯作者：
Stoye, JP
DOI：
10.1098/rspb.2002.1975
发表时间：
2002-05-07
影响因子：
4.7
作者：
Hiendleder, S;Kaupe, B;Janke, A
通讯作者：
Janke, A
影响因子：
5.4
作者：
Alberti, A;Murgia, C;Palmarini, M
通讯作者：
Palmarini, M
影响因子：
5.4
作者：
Dirks, C;Duh, FM;Miller, AD
通讯作者：
Miller, AD