An anti-HIV-1 compound that increases steady-state expression of apoplipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G
An anti-HIV-1 compound that increases steady-state expression of apoplipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G
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DOI：
10.3892/ijmm.2011.737
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发表时间：
2011-10-01
影响因子：
5.4
通讯作者：
Fujita, Mikako
中科院分区：
文献类型：
--
作者：
Ejima, Tomohiko;Hirota, Mayuko;Fujita, Mikako
人载脂蛋白B基因编码酶催化多肽样(APOBEC)3G(A3G)是一种能阻断HIV-1复制的抗病毒蛋白。然而，A3G的抗病毒活性被HIV-1蛋白Vif所克服。Vif的这种抑制功能与其在蛋白酶体中降解A3G的能力有关。这一发现促使我们研究了4-(dimethylamino)-2，6-bis[(N-(2-[(2-nitrophenyl)dithio]ethyl)amino)methyl]pyridine(SN-2)和SN-3的活性。我们发现，5 mU M SN-2使A3G的表达增加到比没有Vif时高得多的水平，而不影响Vif的表达水平。蛋白酶体抑制剂MG-132可提高A3G和VIF的表达水平。这些结果表明，A3G在蛋白酶体中被Vif以外的因素泛素化和降解，SN-2选择性地抑制这些过程。此外，5亩M SN-2对野生型HIV-1的MAGI细胞感染力有明显的抑制作用。这些发现可能有助于开发一种新型的抗HIV-1药物。
Human apoplipoprotein B mRNA-editing enzyme-catalytic polypepticle-like (APOBEC) 3G (A3G) is an antiviral protein that blocks HIV-1 replication. However, the antiviral activity of A3G is overcome by the HIV-1 protein Vif. This inhibitory function of Vif is related to its ability to degrade A3G in the proteasome. This finding prompted us to examine the activities of 4-(dimethylamino)-2,6-bis[(N-(2-[(2-nitrophenyl)dithio]ethyl)amino)methyl]pyridine (SN-2) and SN-3. We found that 5 mu M SN-2 increases the expression of A3G to a level much higher than that observed in the absence of Vif, without affecting the level of Vif expression. The proteasome inhibitor MG-132 increased the level of both A3G and Vif expression. These results demonstrate that A3G is ubiquitinated and degraded in the proteasome by a factor other than Vif, and that SN-2 selectively inhibits these processes. Furthermore, 5 mu M SN-2 significantly inhibited the MAGI cell infectivity of wild-type HIV-1. These findings may contribute to the development of a novel anti-HIV-1 drug.