Division of Medical Biotechnology, Paul-Ehrlich-Institut, 63225 Langen, Germany.
J Biol Chem. 2010 Apr 16;285(16):12248-54. doi: 10.1074/jbc.M109.090977. Epub 2010 Feb 23.
The accessory protein Vpx is encoded by lentiviruses of the human immunodeficiency virus type 2 (HIV-2) and the simian immunodeficiency SIVsm/SIVmac lineage. It is packaged into virions and is indispensable in early steps of monocyte infection. HIV-1, which does not encode Vpx, is not able to infect human monocytes, but Vpx enables infection with HIV-1. The underlying mechanism is not completely understood. In this work, we focus on Vpx-mediated intracellular postentry events as counteraction of host cell proteins. We found that Vpx binds to apolipoprotein B mRNA-editing catalytic polypeptide 3 family member A (APOBEC3A; A3A), a member of the family of cytidine deaminases, present in monocytes. This interaction led to a reduction of the steady-state protein level of A3A. A single-point mutation in Vpx (H82A) abrogated binding to A3A and single-round infection of monocytes by HIV-1. Taken together, our data indicate that lentiviral Vpx counteracts A3A in human monocytes.
辅助蛋白 Vpx 由人类免疫缺陷病毒 2 型 (HIV-2) 和灵长类免疫缺陷 SIVsm/SIVmac 谱系的慢病毒编码。它被包装到病毒粒子中，在单核细胞感染的早期步骤中不可或缺。不编码 Vpx 的 HIV-1 无法感染人类单核细胞，但 Vpx 使 HIV-1 能够感染。其潜在机制尚未完全理解。在这项工作中，我们专注于 Vpx 介导的细胞内进入后事件，作为对宿主细胞蛋白的拮抗作用。我们发现 Vpx 与载脂蛋白 B mRNA 编辑酶催化多肽 3 家族成员 A（APOBEC3A；A3A）结合，A3A 是胞嘧啶脱氨酶家族的一员，存在于单核细胞中。这种相互作用导致 A3A 的稳态蛋白水平降低。Vpx 中的单点突变 (H82A) 消除了与 A3A 的结合以及 HIV-1 对单核细胞的单轮感染。总之，我们的数据表明，慢病毒 Vpx 在人类单核细胞中拮抗 A3A。
