The antiretroviral potency of APOBEC1 deaminase from small animal species
The antiretroviral potency of APOBEC1 deaminase from small animal species
复制标题
DOI：
10.1093/nar/gkn802
复制
发表时间：
2008-12-01
影响因子：
14.9
通讯作者：
Koito, Atsushi
中科院分区：
文献类型：
--
作者：
Ikeda, Terumasa;Ohsugi, Takeo;Koito, Atsushi
尽管 APOBEC3 依赖性逆转录元件限制系统作为针对人类免疫缺陷病毒 1 型 (HIV-1) 感染的内在免疫防御的作用日益明确，但迄今为止，只有哺乳动物 APOBEC1 (A1) 的大鼠直系同源物被证明具有抗病毒活性。在这里，我们从小动物物种中克隆了 A1 cDNA，结果表明，与大鼠 A1 类似，野生型和 vif HIV-1 感染均被小鼠和仓鼠 A1 抑制（4 至 10 倍），而人类 A1 的影响可以忽略不计。此外，兔 A1 显着降低了 HIV-1 病毒颗粒的感染性（300 倍）以及 SIVmac、SIVagm、FIV 和鼠白血病病毒的感染性。免疫印迹分析表明，A1 被有效地整合到 HIV-1 病毒颗粒中，并且它们的包装是通过与核衣壳 Gag 结构域的相互作用介导的。有趣的是，在它们存在的情况下产生的 HIV-1 基因组 RNA 中明显积累了特定的 C-T 变化，而前病毒 DNA 中几乎没有 G-A 变化。总之，这些数据表明 A1 可能作为一种防御机制发挥作用，调节多种哺乳动物物种中的逆转录因子。
Although the role of the APOBEC3-dependent retroelement restriction system as an intrinsic immune defense against human immunodeficiency virus type1 (HIV-1) infection is becoming clear, only the rat ortholog of mammalian APOBEC1s (A1) thus far has been shown to possess antiviral activity. Here, we cloned A1 cDNAs from small animal species, and showed that similar to rat A1, both wild-type and vif HIV-1 infection was inhibited by mouse and hamster A1 (4- to 10-fold), whereas human A1 had negligible effects. Moreover, rabbit A1 significantly reduced the infectivity of both HIV-1 virions (300-fold), as well as that of SIVmac, SIVagm, FIV and murine leukemia virus. Immunoblot analysis showed that A1s were efficiently incorporated into the HIV-1 virion, and their packaging is mediated through an interaction with the nucleocapsid Gag domain. Interestingly, there was a clear accumulation of particular C-T changes in the genomic RNAs of HIV-1 produced in their presence, with few G-A changes in the proviral DNA. Together, these data reveal that A1 may function as a defense mechanism, regulating retroelements in a wide range of mammalian species.