APOBEC3G cytidine deaminase inhibits retrotransposition of endogenous retroviruses
APOBEC3G cytidine deaminase inhibits retrotransposition of endogenous retroviruses
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DOI：
10.1038/nature03238
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发表时间：
2005-01-27
期刊：
影响因子：
64.8
通讯作者：
Schwartz, O
中科院分区：
文献类型：
--
作者：
Esnault, C;Heidmann, O;Schwartz, O
内源性逆转录病毒是一种多拷贝逆转录元件，占小鼠或人类基因组的近10%(1，2)。这些逆转录元件在数百万年前传播到我们的祖先基因组中，并成为基因组进化的驱动力(2-4)。内源性逆转录病毒也可能对宿主有害，并与癌症和自身免疫性疾病有关(5)。由于失活突变的积累，大多数逆转录元件已经失去了复制能力，但包括一些小鼠脑池内A粒子(IAP)和MUDS序列在内的一些逆转录元件仍然是可移动的(6，7)。这些元件编码逆转录酶活性，并通过逆转录转座移动，这是一种涉及RNA中间体的细胞内复制和粘贴过程。宿主已经发展出抑制其表达的机制，主要是共抑制和基因甲基化(4，8)。在这里，我们确定了另一种水平的抗病毒控制，由APOBEC3G介导，APOBEC3G是胞苷脱氨酶家族的成员，以前被证明可以阻止HIV的复制(9-12)。我们发现APOBEC3G显著抑制IAP和MU.S.元件的逆转录转座，并诱导它们的DNA拷贝G-to-A超突变。APOBEC3G通过编辑病毒遗传物质，提供了一种针对内源性和外源性入侵者的祖先广泛的细胞防御。
Endogenous retroviruses are multicopy retroelements accounting for nearly 10% of murine or human genomes(1,2). These retroelements spread into our ancestral genome millions of years ago and have acted as a driving force for genome evolution(2-4). Endogenous retroviruses may also be deleterious for their host, and have been implicated in cancers and autoimmune diseases(5). Most retroelements have lost replication competence because of the accumulation of inactivating mutations, but several, including some murine intracisternal A-particle (IAP) and MusD sequences, are still mobile(6,7). These elements encode a reverse transcriptase activity and move by retrotransposition, an intracellular copy-and-paste process involving an RNA intermediate. The host has developed mechanisms to silence their expression, mainly cosuppression and gene methylation(4,8). Here we identify another level of antiviral control, mediated by APOBEC3G, a member of the cytidine deaminase family that was previously shown to block HIV replication(9-12). We show that APOBEC3G markedly inhibits retrotransposition of IAP and MusD elements, and induces G-to-A hypermutations in their DNA copies. APOBEC3G, by editing viral genetic material, provides an ancestral wide cellular defence against endogenous and exogenous invaders.