Exosomes Packaging APOBEC3G Confer Human Immunodeficiency Virus Resistance to Recipient Cells
Exosomes Packaging APOBEC3G Confer Human Immunodeficiency Virus Resistance to Recipient Cells
复制标题
DOI：
10.1128/jvi.01658-08
复制
发表时间：
2009-01-15
影响因子：
5.4
通讯作者：
Popik, Waldemar
中科院分区：
文献类型：
--
作者：
Khatua, Atanu K.;Taylor, Harry E.;Popik, Waldemar
人胞苷脱氨酶APOBEC3G （A3G）是抵抗人类免疫缺陷病毒1型（HIV-1）和其他逆转录病毒的细胞防御系统的一部分。在HIV-1蛋白Vif的存在下，A3G的抗逆转录病毒活性会严重减弱。然而，在一些表达酶活性低分子质量形式A3G的细胞中，HIV-1的复制在Vif积累之前的整合前阶段受到限制。在这里，我们发现A3G可以由外泌体中的细胞分泌，赋予外泌体受体细胞对病毒缺陷型和野生型HIV-1的抗性。我们的研究结果还表明，A3G是外泌体抗hiv -1活性的主要外泌体成分。然而，酶修饰的A3G的酶活性与HIV-1 DNA中观察到的有限胞苷脱胺不相关，这表明A3G负载的外泌体通过非酶机制限制HIV-1。实时荧光定量PCR结果表明，A3G外泌体减少了HIV-1逆转录产物的积累，降低了HIV-1 Gag和Vif蛋白的稳态水平。我们的研究结果表明，A3G外泌体可以发展成为一类新的抗hiv -1治疗药物。
The human cytidine deaminase APOBEC3G (A3G) is a part of a cellular defense system against human immunodeficiency virus type 1 (HIV-1) and other retroviruses. Antiretroviral activity of A3G can be severely blunted in the presence of the HIV-1 protein Vif. However, in some cells expressing the enzymatically active low-molecular-mass form of A3G, HIV-1 replication is restricted at preintegration steps, before accumulation of Vif. Here, we show that A3G can be secreted by cells in exosomes that confer resistance to both vif-defective and wild-type HIV-1 in exosome recipient cells. Our results also suggest that A3G is the major exosomal component responsible for the anti-HIV-1 activity of exosomes. However, enzymatic activity of encapsidated A3G does not correlate with the observed limited cytidine deamination in HIV-1 DNA, suggesting that A3G-laden exosomes restrict HIV-1 through a nonenzymatic mechanism. Real-time PCR quantitation demonstrated that A3G exosomes reduce accumulation of HIV-1 reverse transcription products and steady-state levels of HIV-1 Gag and Vif proteins. Our findings suggest that A3G exosomes could be developed into a novel class of anti-HIV-1 therapeutics.