Early and transient reverse transcription during primary deltaretroviral infection of sheep.
Early and transient reverse transcription during primary deltaretroviral infection of sheep.
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DOI：
10.1186/1742-4690-5-16
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发表时间：
2008-02-01
期刊：
影响因子：
3.3
通讯作者：
Mortreux F
中科院分区：
文献类型：
--
作者：
Pomier C;Alcaraz MT;Debacq C;Lançon A;Kerkhofs P;Willems L;Wattel E;Mortreux F
个体内遗传变异在动物和人类中的δ逆转录病毒复制和相关白血病发生中起着重要作用。迄今为止，这些病毒的复制仅在感染的慢性期期间进行了研究，此时它们主要通过其宿主细胞的克隆扩增进行传播，通过体细胞突变过程而变化，没有证据表明逆转录酶（RT）相关的取代。新生物体的初次感染需要涉及同种异体细胞感染，从而涉及逆转录。在这里，我们证明，主要实验牛白血病病毒（BLV）感染的绵羊显示早期和强烈的水平复制传播的病毒产生频繁的RT相关的替换，占体内BLV的遗传变异的69%，在感染的前8个月的爆发。在此期间，已发现突变序列的细胞间传代和经历RT相关突变和体细胞突变的序列的证据。RT依赖性前病毒替代的检测限于一个狭窄的窗口，包括血清转化后的前250天。与慢病毒相反，δ逆转录病毒显示出两种时间依赖性遗传变异机制，与其体内复制的两步性质平行。我们认为，早期和短暂的RT水平复制有助于病毒逃避宿主免疫反应的第一波，而持续克隆扩增过程中体细胞依赖的遗传变异性有助于感染的克隆逃避持久和强烈的免疫压力，其特征是慢性阶段的deltaretrovirusinfection。
Intraindividual genetic variability plays a central role in deltaretrovirus replication and associated leukemogenesis in animals as in humans. To date, the replication of these viruses has only been investigated during the chronic phase of the infection when they mainly spread through the clonal expansion of their host cells, vary through a somatic mutation process without evidence for reverse transcriptase (RT)-associated substitution. Primary infection of a new organism necessary involves allogenic cell infection and thus reverse transcription. Here we demonstrate that the primary experimental bovine leukemia virus (BLV) infection of sheep displays an early and intense burst of horizontal replicative dissemination of the virus generating frequent RT-associated substitutions that account for 69% of the in vivo BLV genetic variability during the first 8 months of the infection. During this period, evidence has been found of a cell-to-cell passage of a mutated sequence and of a sequence having undergone both RT-associated and somatic mutations. The detection of RT-dependent proviral substitution was restricted to a narrow window encompassing the first 250 days following seroconversion. In contrast to lentiviruses, deltaretroviruses display two time-dependent mechanisms of genetic variation that parallel their two-step nature of replication in vivo. We propose that the early and transient RT-based horizontal replication helps the virus escape the first wave of host immune response whereas somatic-dependent genetic variability during persistent clonal expansion helps infected clones escape the persistent and intense immune pressure that characterizes the chronic phase of deltaretrovirus infection.
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影响因子：
3.1
作者：
Florins, Arnaud;Gillet, Nicolas;Willems, Luc
通讯作者：
Willems, Luc
DOI：
10.1073/pnas.89.15.6919
发表时间：
1992-08-01
影响因子：
11.1
作者：
BOYER, JC;BEBENEK, K;KUNKEL, TA
通讯作者：
KUNKEL, TA
影响因子：
2.9
作者：
JI, JP;LOEB, LA
通讯作者：
LOEB, LA
影响因子：
3.7
作者：
Laakso, Meg M.;Sutton, Richard E.
通讯作者：
Sutton, Richard E.
DOI：
10.1073/pnas.90.9.4171
发表时间：
1993-05-01
影响因子：
11.1
作者：
DRAKE, JW
通讯作者：
DRAKE, JW