Chang Y Y, Yu S L, Syu W J
Institute of Microbiology and Immunology, National Yang Ming University, Taipei, Taiwan, ROC.
J Biomed Sci. 1999 Sep-Oct;6(5):333-41. doi: 10.1007/BF02253522.
The HIV pol sequentially encodes protease (PR), reverse transcriptase (RT), and integrase (IN) from the 5'-3' direction. We explored the significance of this gene arrangement. All six possible gene dispositions were examined. In two situations where PR was removed from the leading place and no two genes were in their original location, viral polyprotein processing was abolished. Processing of the polyprotein did not occur when IN was translocated to the front of PR-RT. However, in the following two arrangements, the polyprotein was processed but only at specific sites. First, PR remained in the leading position while the locations of RT and IN were exchanged; viral polyprotein was processed at a site between the upstream transframe peptide (TF) and PR. Second, PR was placed after RT-IN and located at the distal end of Pol. Processing occurred only at the created junction between TF and RT. These results indicated that cleavage after TF occurred autocatalytically but did not proceed to a second site, which needed an extraneous PR for trans-action. Therefore, arranging Pol in the order of PR-RT-IN warrants the streamline processing of the polyprotein once the autocleavage is initiated.
HIV的pol基因从5'-3'方向依次编码蛋白酶（PR）、逆转录酶（RT）和整合酶（IN）。我们探究了这种基因排列的意义。研究了所有六种可能的基因排列方式。在两种情况下，PR被从首位移除且没有两个基因处于其原始位置，病毒多聚蛋白的加工被废除。当IN被转移到PR-RT的前面时，多聚蛋白的加工未发生。然而，在接下来的两种排列中，多聚蛋白被加工但仅在特定位点。首先，PR保留在首位，而RT和IN的位置互换；病毒多聚蛋白在上游移码肽（TF）和PR之间的一个位点被加工。其次，PR被置于RT-IN之后并位于Pol的末端。加工仅发生在TF和RT之间产生的连接处。这些结果表明TF之后的切割是自动催化的，但不会进行到第二个位点，而第二个位点需要一个外部的PR进行反式作用。因此，按照PR-RT-IN的顺序排列Pol保证了一旦自动切割开始，多聚蛋白就能进行流水线式加工。
