...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The antiretroviral activity of APOBEC3 is inhibited by the foamy virus accessory Bet protein
【24h】

The antiretroviral activity of APOBEC3 is inhibited by the foamy virus accessory Bet protein

机译：泡沫病毒辅助蛋白Bet蛋白抑制APOBEC3的抗逆转录病毒活性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Genome hypermutation of different orthoretroviruses by cellular cytidine deaminases of the APOBEC3 family during reverse transcription has recently been observed. Lentiviruses like HIV-1 have acquired proteins preventing genome editing in the newly infected cell. Here we show that feline foamy virus (FFV), a typical member of the foamy retrovirus subfamily Spumaretrovirinae, is also refractory to genome deamination. APOBEC3-like FFV genome editing in APOBEC3-positive feline CRFK cells only occurs when the accessory FFV Bet protein is functionally inactivated. Editing of bet-deficient FFV genomes is paralleled by a strong decrease in FFV titer. In contrast to lentiviruses, cytidine deamination already takes place in APOBEC3-positive FFV-producing cells, because edited proviral DNA genomes are consistently present in released particles. By cloning the feline APOBEC3 orthologue, we found that its homology to the second domain of human APOBEC3F is 48%. Expression of feline APOBEC3 in APOBEC3-negative human 293T cells reproduced the effects seen in homologous CRFK cells: Bet-deficient FFV displayed severely reduced titers, high-level genome editing, reduced particle release, and suppressed Gag processing. Although WT Bet efficiently preserved FFV infectivity and genome integrity, it sustained particle release and Gag processing only when fe3 was moderately expressed. Similar to lentiviral Vif proteins, FFV Bet specifically bound feline APOBEC3. In particles from Bet-deficient FFV, feline APOBEC3 was clearly present, whereas its foamy viral antagonist Bet was undetectable in purified WT particles. This is the first report that, in addition to lentiviruses, the foamy viruses also developed APOBEC3-counter-acting proteins.
机译：最近已经观察到在逆转录过程中，APOBEC3家族的细胞胞嘧啶脱氨酶使不同的正逆转录病毒的基因组超突变。像HIV-1这样的慢病毒已经获得了阻止新感染细胞中基因组编辑的蛋白质。在这里，我们显示猫泡沫状病毒（FFV），泡沫逆转录病毒亚家族Spumaretrovirinae的典型成员，对基因组脱氨也具有抵抗力。仅当辅助FFV Bet蛋白功能失活时，才会在APOBEC3阳性猫CRFK细胞中进行类似APOBEC3的FFV基因组编辑。缺乏赌注的FFV基因组的编辑与FFV效价的大幅降低并行。与慢病毒相反，胞嘧啶脱氨已经在APOBEC3阳性FFV产生细胞中发生，因为经过编辑的原病毒DNA基因组始终存在于释放的颗粒中。通过克隆猫APOBEC3直向同源物，我们发现它与人APOBEC3F第二个域的同源性为48％。猫APOBEC3在APOBEC3阴性的人293T细胞中的表达重现了在同源CRFK细胞中看到的效果：缺蛋白的FFV显着降低了效价，高水平的基因组编辑，减少了颗粒释放并抑制了Gag加工。尽管WT Bet有效地保留了FFV的感染性和基因组完整性，但只有在适度表达fe3时，它才能维持颗粒释放和Gag处理。类似于慢病毒Vif蛋白，FFV Bet特异性结合猫APOBEC3。在缺乏Bet的FFV的颗粒中，明显存在猫APOBEC3，而在纯化的WT颗粒中未检测到其泡沫病毒拮抗剂Bet。这是第一个报道，除了慢病毒之外，泡沫病毒还产生了APOBEC3反作用蛋白。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

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