Center for AIDS Health Disparities Research, Meharry Medical College, 1005 D. B. Todd Blvd., Nashville, TN 37208, USA.
Virology. 2010 Apr 25;400(1):68-75. doi: 10.1016/j.virol.2010.01.021. Epub 2010 Feb 11.
Human cytidine deaminases, including APOBEC3G (A3G) and A3F, are part of a cellular defense system against retroviruses and retroelements including non-LTR retrotransposons LINE-1 (L1) and Alu. Expression of cellular A3 proteins is sufficient for inhibition of L1 and Alu retrotransposition, but the effect of A3 proteins transferred in exosomes on retroelement mobilization is unknown. Here, we demonstrate for the first time that exosomes secreted by CD4(+)H9 T cells and mature monocyte-derived dendritic cells encapsidate A3G and A3F and inhibit L1 and Alu retrotransposition. A3G is the major contributor to the inhibitory activity of exosomes, however, the contribution of A3F in H9 exosomes cannot be excluded. Additionally, we show that exosomes encapsidate mRNAs coding for A3 proteins. A3G mRNA, and less so A3F, was enriched in exosomes secreted by H9 cells. Exosomal A3G mRNA was functional in vitro. Whether exosomes inhibit retrotransposons in vivo requires further investigation.
人类胞嘧啶脱氨酶，包括 APOBEC3G（A3G）和 A3F，是细胞防御系统的一部分，可抵御包括非 LTR 反转录转座子 LINE-1（L1）和 Alu 在内的逆转录病毒和 retroelements。细胞 A3 蛋白的表达足以抑制 L1 和 Alu 反转录转座，但外泌体中转移的 A3 蛋白对 retroelement 动员的影响尚不清楚。在这里，我们首次证明，CD4(+)H9 T 细胞和成熟单核细胞衍生的树突状细胞分泌的外泌体包裹 A3G 和 A3F，并抑制 L1 和 Alu 反转录转座。A3G 是外泌体抑制活性的主要贡献者，然而，不能排除 A3F 在 H9 外泌体中的作用。此外，我们还表明，外泌体包裹编码 A3 蛋白的 mRNAs。A3G mRNA，而 A3F 则较少，在 H9 细胞分泌的外泌体中富集。外泌体 A3G mRNA 在体外具有功能。外泌体是否在体内抑制 retrotransposons 需要进一步研究。
