期刊
BMC MICROBIOLOGY
卷 22, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12866-022-02503-3
关键词
HIV-1; Protease; Gag; Gag-Pol; Gag cleavage; Virus assembly
类别
资金
- Taipei Veterans General Hospital [V106C-047, V107C-049, V108C-034]
- Taiwan Ministry of Science and Technology [106-2320-B-010-017-MY2, 108-2320-B-010-030]
The amount of HIV-1 Gag-Pol or Pol viral incorporation is largely dependent on virus particle production, and cleavage blocking in the Gag-Pol N-terminal Gag domain does not exert significant impacts on Pol packaging.
Background HIV-1 pol, which encodes enzymes required for virus replication, is initially translated as a Gag-Pol fusion protein. Gag-Pol is incorporated into virions via interactions with Gag precursor Pr55(gag). Protease (PR) embedded in Gag-Pol mediates the proteolytic processing of both Pr55gag and Gag-Pol during or soon after virus particle release from cells. Since efficient Gag-Pol viral incorporation depends on interaction with Pr55(gag) via its N-terminal Gag domain, the prevention of premature Gag cleavage may alleviate Gag-Pol packaging deficiencies associated with cleavage enhancement from PR. Results We engineered PR cleavage-blocking Gag mutations with the potential to significantly reduce Gag processing efficiency. Such mutations may mitigate the negative effects of enhanced PR activation on virus assembly and Gag-Pol packaging due to an RT dimerization enhancer or leucine zipper dimerization motif. When co-expressed with Pr55(gag), we noted that enhanced PR activation resulted in reduced Gag-Pol cis or trans incorporation into Pr55(gag) particles, regardless of whether or not Gag cleavage sites within Gag-Pol were blocked. Conclusions Our data suggest that the amount of HIV-1 Gag-Pol or Pol viral incorporation is largely dependent on virus particle production, and that cleavage blocking in the Gag-Pol N-terminal Gag domain does not exert significant impacts on Pol packaging.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据