Murine retrovirus escapes from murine APOBEC3 via two distinct novel mechanisms
Murine retrovirus escapes from murine APOBEC3 via two distinct novel mechanisms
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DOI：
10.1016/j.cub.2006.06.055
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发表时间：
2006-08-08
期刊：
影响因子：
9.2
通讯作者：
Uchiyama, Takashi
中科院分区：
文献类型：
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作者：
Abudu, Aierken;Takaori-Kondo, Akifumi;Uchiyama, Takashi
APOBEC3G （A3G）是一种抗逆转录病毒宿主因子，其功能是将逆转录病毒cDNA中的dC脱氨为dU[1-5]。HIV-1 Vif蛋白通过泛素-蛋白酶体途径对抗A3G[6-12]。对于简单的逆转录病毒，如小鼠白血病病毒（MLV），尽管它不具有任何辅助蛋白如Vif，但它为何能在表达APOBEC3 （A3）的细胞中复制，目前尚不清楚[2,13]。在这项研究中，我们证明了MLV通过两种不同的新机制从小鼠A3 （mA3）中逃逸。首先，病毒RNA （vRNA）阻断mA3与Gag的结合，导致mA3被排除在MLV病毒粒子之外。其次，病毒蛋白酶（vPR）在病毒粒子成熟后切割mA3。在这里，我们认为每种病毒都有自己的逃离A3蛋白的策略，这些机制可能被其他不具有vif样蛋白的病毒所使用。另一方面，小鼠具有另一种形式的mA3， Delta外显子5，通过vPR逃脱切割，显示出比野生型mA3更强的抗病毒活性。这也表明，宿主内在免疫和病毒之间的斗争导致了双方蛋白质的进化。
APOBEC3G (A3G) is an antiretroviral host factor that functions by deaminating dC to dU in retroviral cDNA [1-5]. HIV-1 Vif protein counteracts A3G via a ubiquitin-proteasome pathway [6-12]. In the case of a simple retrovirus such as the murine leukemia virus (MLV), it remains unclear why it can replicate in cells expressing APOBEC3 (A3) even though it doesn't possess any accessory proteins such as Vif [2,13]. In this study, we demonstrate that MLV escapes from murine A3 (mA3) via two distinct novel mechanisms. First, viral RNA (vRNA) blocks the binding of mA3 to Gag, resulting in the exclusion of mA3 from MLV virions. Second, viral protease (vPR) cleaves mA3 after maturation of virions. Here, we suggest that each virus has its own strategy to escape from A3 proteins and that these mechanisms might be used by other viruses that do not possess Vif-like protein. On the other hand, mice possess another form of mA3, Delta exon5, that escapes from the cleavage by vPR to show more antiviral activity than the wild type mA3. This also suggests that battles between host intrinsic immunity and viruses have led to the evolution of proteins on both sides.