Mechanistic features of recombination in HIV.
Mechanistic features of recombination in HIV.
复制标题
DOI：
--
复制
发表时间：
2005-04
期刊：
影响因子：
2.2
通讯作者：
R. Galetto;M. Negroni
中科院分区：
文献类型：
--
作者：
R. Galetto;M. Negroni
重组在逆转录病毒进化中的重要性已经被承认了几十年。因此，在确定HIV为艾滋病的病原后，人们怀疑重组也可能在这种病毒的进化中发挥核心作用。然而，直到最近，对全球HIV感染的广泛流行病学研究才提供了体内重组发生的估计，揭示了重组频率，使最初的预期相形见绌。如今，重组被认为是这种逆转录病毒感染周期的一个组成部分，它影响着感染的诊断和治疗，特别是当基因上遥远的病毒已经成为重组形式的起源时。逆转录病毒重组是当两个遗传上不同的基因组RNA分子存在于同一病毒颗粒中时观察到的，并且发生在逆转录步骤中。这篇综述的重点是已经提出的解释逆转录病毒中重组发生的机制，从链位移模型来看，重组发生在第二DNA链合成过程中；到描述在第一DNA链合成过程中负责复制选择重组的因素，例如基因组RNA中断裂、暂停位点或二级结构的存在。这些模型中的大多数都得到了来自体外重组系统或使用学术模型序列的细胞感染研究的实验数据的支持。体内的情况预计会更加复杂，因为当重组涉及相对较远的分离株时，就像亚型间重组的情况一样，有几个因素起作用。目前，很明显需要进一步的研究来评估体内重组是否存在一种普遍的机制，这些研究对于理解重组的潜在机制如何促进HIV的进化也至关重要。
The importance of recombination in retroviral evolution has been acknowledged for several decades. Consequently, after the identification of HIV as the etiological agent of AIDS, it was suspected that recombination could also play a central role in the evolution of this virus. However, only recently, extensive epidemiologic studies of HIV infections worldwide have provided an estimate for the occurrence of recombination in vivo, unveiling recombination frequencies that dwarf those initially expected. Nowadays, recombination is regarded as an integral part of the infectious cycle of this retrovirus, which impacts on diagnosis and treatment of infections, especially when genetically distant viruses have been at the origin of the recombinant forms. Retroviral recombination is observed when two genetically divergent genomic RNA molecules are present in the same viral particle, and arises during the reverse transcription step. This review focuses on the mechanisms that have been proposed to account for the occurrence of recombination in retroviruses, from the strand displacement model, according to which recombination occurs during second DNA strand synthesis; to the description of the factors responsible for copy-choice recombination during first DNA strand synthesis, such as the presence of breaks, pause sites, or secondary structures in the genomic RNA. Most of these models have been supported by experimental data obtained from in vitro reconstituted systems or from cell infection studies using academic model sequences. The situation in vivo is expected to be more complex, since several factors come into play when recombination involves relatively distant isolates, as in the case of inter-subtype recombination. At present, it is clear that further studies are needed in order to evaluate whether a prevailing mechanism exists for in vivo recombination, and these studies will also be essential for understanding how the underlying mechanisms of recombination contribute to the evolution of HIV.