Abudu Aierken, Takaori-Kondo Akifumi, Izumi Taisuke, Shirakawa Kotaro, Kobayashi Masayuki, Sasada Amane, Fukunaga Keiko, Uchiyama Takashi
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaracho, Sakyo-ku, Kyoto 606-8507, Japan.
Curr Biol. 2006 Aug 8;16(15):1565-70. doi: 10.1016/j.cub.2006.06.055.
APOBEC3G (A3G) is an antiretroviral host factor that functions by deaminating dC to dU in retroviral cDNA. HIV-1 Vif protein counteracts A3G via a ubiquitin-proteasome pathway. 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. 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.
载脂蛋白B mRNA编辑酶催化多肽样蛋白3G（A3G）是一种抗逆转录病毒宿主因子，通过将逆转录病毒cDNA中的胞嘧啶脱氨基为尿嘧啶发挥作用。HIV-1病毒感染因子（Vif）蛋白通过泛素-蛋白酶体途径对抗A3G。对于像鼠白血病病毒（MLV）这样的简单逆转录病毒，尽管它不具备任何诸如Vif之类的辅助蛋白，但它为何能在表达载脂蛋白B mRNA编辑酶催化多肽样蛋白3（A3）的细胞中复制仍不清楚。在本研究中，我们证明MLV通过两种不同的新机制逃避鼠A3（mA3）。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。在此，我们认为每种病毒都有其自身逃避A3蛋白的策略，并且这些机制可能被其他不具备类似Vif蛋白的病毒所采用。另一方面，小鼠拥有另一种形式的mA3，即δ外显子5，它能逃避vPR的切割，从而比野生型mA3表现出更强的抗病毒活性。这也表明宿主固有免疫与病毒之间的斗争导致了双方蛋白质的进化。
