APOBEC3 inhibits mouse mammary tumour virus replication in vivo
APOBEC3 inhibits mouse mammary tumour virus replication in vivo
复制标题
DOI：
10.1038/nature05540
复制
发表时间：
2007-02-22
期刊：
影响因子：
64.8
通讯作者：
Ross, Susan R.
中科院分区：
文献类型：
--
作者：
Okeoma, Chioma M.;Lovsin, Nika;Ross, Susan R.
所有哺乳动物的基因组都编码apobec 3基因，该基因被认为对包括人类免疫缺陷病毒1型（HIV-1）在内的几种病毒具有内在细胞免疫功能（1）。APOBEC 3（A3）蛋白被包装到病毒体中，并在新感染的细胞中抑制逆转录病毒复制，至少部分通过脱氨基负链DNA中间体上的胞苷（2）。然而，A3在对小鼠逆转录病毒的先天抗性中的作用尚不清楚。在这里，我们表明，A3的功能在体内逆转录病毒感染，并提供部分保护小鼠免受感染小鼠乳腺肿瘤病毒（MMTV）。小鼠A3和人A3 G蛋白都以RNA依赖的方式与MMTV核衣壳相互作用，并被包装成病毒体。此外，小鼠含A3和人含A3 G的病毒粒子显示滴度显著降低。最后，A3（-/-）小鼠更容易感染MMTV，因为病毒传播比野生型小鼠更迅速和广泛。
Genomes of all mammals encode apobec3 genes, which are thought to have a function in intrinsic cellular immunity to several viruses including human immunodeficiency virus type 1 (HIV-1)(1). APOBEC3 (A3) proteins are packaged into virions and inhibit retroviral replication in newly infected cells, at least in part by deaminating cytidines on the negative strand DNA intermediates(2). However, the role of A3 in innate resistance to mouse retroviruses is not understood. Here we show that A3 functions during retroviral infection in vivo and provides partial protection to mice against infection with mouse mammary tumour virus ( MMTV). Both mouse A3 and human A3G proteins interacted with the MMTV nucleocapsid in an RNA-dependent fashion and were packaged into virions. In addition, mouse A3-containing and human A3G-containing virions showed a marked decrease in titre. Last, A3(-/-) mice were more susceptible to MMTV infection, because virus spread was more rapid and extensive than in their wild-type littermates.