Enhanced replication and pathogenesis of Moloney murine leukemia virus in mice defective in the murine APOBEC3 gene
Enhanced replication and pathogenesis of Moloney murine leukemia virus in mice defective in the murine APOBEC3 gene
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DOI：
10.1016/j.virol.2008.11.051
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发表时间：
2009-03-15
期刊：
影响因子：
3.7
通讯作者：
Fan, Hung
中科院分区：
文献类型：
--
作者：
Low, Audrey;Okeoma, Chioma M.;Fan, Hung
人APOBEC 3G（hA 3G）是AID/APOBEC脱氨酶家族的成员，是人类免疫缺陷病毒（HIV）的限制因子。在不存在病毒Vif蛋白的情况下，hA 3G被包装到病毒体中，并且在受体细胞中的逆转录期间，它使胞嘧啶脱氨基，导致G-A超突变和病毒DNA的失活。与携带七个APOBEC 3基因的人类不同，小鼠只携带一个，mA 3。因此，可以在基因失活的mA 3-/-敲除小鼠中研究mA 3在限制逆转录病毒感染中的作用。与野生型小鼠相比，M-MuLV感染的mA 3-/-小鼠在非常早期显示出显著更高的感染水平（约100%）。0-10天2个日志）。特别是在骨髓和脾脏中。使用表达增强型水母绿色荧光蛋白（EGFP）的基于M-MuLV的逆转录病毒载体，在表达或缺乏mA 3的原代骨髓来源树突状细胞（BMDC）中离体研究M-MULV感染的限制。结果表明，病毒粒子内的mA 3以及受体细胞中的mA 3有助于BMDCs对感染的抵抗。最后，M-MULV感染的mA 3 +/+小鼠与缺乏一个或两个mA 3拷贝的动物相比，发展白血病的速度更慢，尽管所产生的疾病相似（T淋巴瘤）。这些研究表明，mA 3在体内限制M-MuLV的复制和发病机制。(c)2008爱思唯尔公司版权所有..
Human APOBEC3G (hA3G), a member of the AID/APOBEC family of deaminases, is a restriction factor for human immunodeficiency virus (HIV). In the absence of the viral Vif protein hA3G is packaged into virions and during reverse transcription in a recipient cell it deaminates cytosines, leading to G-A hypermutation and inactivation of the viral DNA. Unlike humans, who carry seven APOBEC3 genes, mice only carry one, mA3. Thus the role of mA3 in restriction of retroviral infection could be studied in mA3 -/- knockout mice, where the gene is inactivated. M-MuLV-infected mA3 -/- mice showed substantially higher levels of infection at very early times compared to wild-type mice (ca. 2 logs at 0-10 days). particularly in the bone marrow and spleen. Restriction Of M-MULV infection was Studied ex vivo in primary bone marrow-derived dendritic cells (BMDCs) that express or lack mA3, using an M-MuLV-based retroviral vector expressing enhanced jellyfish green fluorescent protein (EGFP). The results indicated that mA3 within the virions as well as mA3 in the recipient cell contribute to resistance to infection in BMDCs. Finally, M-MULV-infected mA3 +/+ mice developed leukemia more slowly compared to animals lacking one or both copies of mA3 although the resulting disease was similar (T-lymphoma). These Studies indicate that mA3 restricts replication and pathogenesis of M-MuLV in vivo. (c) 2008 Elsevier Inc All rights reserved..