• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Journal of Virology >HIV-2 Genome Dimerization Is Required for the Correct Processing of Gag: a Second-Site Reversion in Matrix Can Restore Both Processes in Dimerization-Impaired Mutant Viruses
【2h】

HIV-2 Genome Dimerization Is Required for the Correct Processing of Gag: a Second-Site Reversion in Matrix Can Restore Both Processes in Dimerization-Impaired Mutant Viruses

机译：HIV-2基因组二聚化是正确处理gag所必需的：基质中的第二位还原可以恢复二聚化受损突变病毒中的两个过程

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

A unique feature of retroviruses is the packaging of two copies of their genome, noncovalently linked at their 5′ ends. In vitro, dimerization of human immunodeficiency virus type 2 (HIV-2) RNA occurs by interaction of a self-complementary sequence exposed in the loop of stem-loop 1 (SL-1), also termed the dimer initiation site (DIS). However, in virions, HIV-2 genome dimerization does not depend on the DIS. Instead, a palindrome located within the packaging signal (Psi) is the essential motif for genome dimerization. We reported previously that a mutation within Psi decreasing genome dimerization and packaging also resulted in a reduced proportion of mature particles (A. L'Hernault, J. S. Greatorex, R. A. Crowther, and A. M. Lever, Retrovirology 4:90, 2007). In this study, we investigated further the relationship between HIV-2 genome dimerization, particle maturation, and infectivity by using a series of targeted mutations in SL-1. Our results show that disruption of a purine-rich (392-GGAG-395) motif within Psi causes a severe reduction in genome dimerization and a replication defect. Maintaining the extended SL-1 structure in combination with the 392-GGAG-395 motif enhanced packaging. Unlike that of HIV-1, which can replicate despite mutation of the DIS, HIV-2 replication depends critically on genome dimerization rather than just packaging efficiency. Gag processing was altered in the HIV-2 dimerization mutants, resulting in the accumulation of the MA-CA-p2 processing intermediate and suggesting a link between genome dimerization and particle assembly. Analysis of revertant SL-1 mutant viruses revealed that a compensatory mutation in matrix (70TI) could rescue viral replication and partially restore genome dimerization and Gag processing. Our results are consistent with interdependence between HIV-2 RNA dimerization and the correct proteolytic cleavage of the Gag polyprotein.
机译：逆转录病毒的独特特征是包装了其基因组的两个副本，在其5'端非共价连接。在体外，人类免疫缺陷病毒2型（HIV-2）RNA的二聚化是通过在茎环1（SL-1）的环中暴露的自身互补序列（也称为二聚体起始位点（DIS））的相互作用而发生的。但是，在病毒体中，HIV-2基因组二聚化不依赖于DIS。相反，位于包装信号（Psi）中的回文是基因组二聚化的基本主题。我们之前曾报道过，Psi内的突变降低了基因组二聚化和包装，也导致了成熟颗粒的比例降低（A.L'Hernault，J.S.Greatorex，R.A.Crowther和A.M.Lever，Retrovirology 4:90，2007）。在这项研究中，我们通过使用SL-1中的一系列靶向突变，进一步研究了HIV-2基因组二聚化，颗粒成熟和感染性之间的关系。我们的结果表明，Psi内富含嘌呤的（392-GGAG-395）基序的破坏会导致基因组二聚化和复制缺陷的严重减少。结合392-GGAG-395图案增强包装，保持扩展的SL-1结构。不同于DIS-1突变后仍可复制的HIV-1，HIV-2复制主要取决于基因组二聚化而不仅仅是包装效率。 gag加工在HIV-2二聚体突变体中发生了变化，导致了MA-CA-p2加工中间体的积累，并暗示了基因组二聚体与颗粒组装之间的联系。对回复性SL-1突变病毒的分析表明，基质（70TI）中的补偿性突变可以挽救病毒复制并部分恢复基因组二聚化和Gag加工。我们的结果与HIV-2 RNA二聚化和Gag多蛋白的正确蛋白水解切割之间的相互依赖性一致。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号