HIV-1 infection-induced alteration of the cellular splicing machinery

病毒在HIV-1感染细胞培养物中的传播速度是快还是慢，即使在今天也仍然无法预测。在宿主细胞特异性影响中，病毒初级转录物的加工，即选择性剪接，起着关键作用。剪接调节宿主细胞蛋白的细胞类型特异性差异及其转录物表型的差异，反过来又可以作为感染的结果而被调节，对病毒复制有重大影响。我们提出，通过感染调节细胞剪接代表了一种尚未被发现的敌意接管机制。本提案的目的是通过对未感染和HIV-1感染细胞的全转录组测序，确定感染诱导的可选剪接事件，这些剪接事件影响细胞转录本的翻译产物i)影响HIV-1剪接和/或ii)病毒复制。比较细胞类型特异性转录组和感染诱导的改变，结合剪接顺式调控元件的不断增加的知识，将汇聚成对HIV-1复制的新的基本理解。

Whether viral spread in an HIV-1 infected cell culture is slow or fast is even nowadays still unpredictable. Among responsible host cell-specific influences processing of the viral primary transcript, i.e., alternative splicing, plays a key role. Cell type specific differences of splicing regulatory host cell proteins and differences in the phenotype of their transcripts, which in turn can be modulated as a consequence of the infection, have a substantial impact on viral replication. We propose that modulating cellular splicing through the infection represents an as-yet-undiscovered way of hostile takeover mechanism. The aim of this proposal is to identify infection-induced alternative splicing events which affect cellular transcripts whose translational products i) influence HIV-1 splicing and/or ii) viral replication by sequencing whole transcriptomes of uninfected and HIV-1-infected cells. Comparing cell-type specific transcriptomes and infection-induced alterations combined with increasing knowledge of splicing cis-regulatory elements will converge into a new fundamental understanding of HIV-1 replication.