Doehle Brian P, Schäfer Alexandra, Cullen Bryan R
Center for Virology, Duke University Medical Center, Durham, NC 27710, USA.
Virology. 2005 Sep 1;339(2):281-8. doi: 10.1016/j.virol.2005.06.005.
While the human antiretroviral defense factors APOBEC3F and APOBEC3G are potent inhibitors of the replication of HIV-1 mutants lacking a functional vif gene, the Vif protein expressed by wild-type HIV-1 blocks the function of both host cell proteins. Here, we report that a third human protein, APOBEC3B, is able to suppress the infectivity of both Vif-deficient and wild-type HIV-1 with equal efficiency. APOBEC3B, which shows approximately 58% sequence identity to both APOBEC3F and APOBEC3G, shares the ability of these other human proteins to bind the nucleocapsid domain of HIV-1 Gag specifically and to thereby package into progeny virion particles. However, APOBEC3B differs from APOBEC3F and APOBEC3G in that it is unable to bind to HIV-1 Vif in co-expressing cells and is therefore efficiently packaged into HIV-1 virions regardless of Vif expression. Unfortunately, APOBEC3B also differs from APOBEC3F and APOBEC3G in that it is not normally expressed in the lymphoid cells that serve as targets for HIV-1 infection. These studies therefore raise the possibility that activation of the endogenous APOBEC3B gene in primary human lymphoid cells could form a novel and effective strategy for inhibition of HIV-1 replication in vivo.
人类抗逆转录病毒防御因子载脂蛋白B mRNA编辑酶催化多肽样3F（APOBEC3F）和载脂蛋白B mRNA编辑酶催化多肽样3G（APOBEC3G）是缺乏功能性病毒感染因子（vif）基因的HIV-1突变体复制的有效抑制剂，而野生型HIV-1表达的Vif蛋白可阻断这两种宿主细胞蛋白的功能。在此，我们报告第三种人类蛋白APOBEC3B能够以相同效率抑制Vif缺陷型和野生型HIV-1的感染性。APOBEC3B与APOBEC3F和APOBEC3G的序列相似度约为58%，它具有与其他人类蛋白相同的能力，即特异性结合HIV-1 Gag的核衣壳结构域，从而包装进子代病毒颗粒中。然而，APOBEC3B与APOBEC3F和APOBEC3G不同，它在共表达细胞中无法与HIV-1 Vif结合，因此无论Vif是否表达，它都能有效地包装进HIV-1病毒体中。不幸的是，APOBEC3B与APOBEC3F和APOBEC3G的另一个不同之处在于，它在作为HIV-1感染靶标的淋巴细胞中通常不表达。因此，这些研究提出了一种可能性，即激活原代人类淋巴细胞中的内源性APOBEC3B基因可能成为体内抑制HIV-1复制的一种新的有效策略。
