Wang Feng-Xiang, Huang Jialing, Zhang Hangxiang, Ma Xinliang, Zhang Hui
Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
J Gen Virol. 2008 Mar;89(Pt 3):722-730. doi: 10.1099/vir.0.83530-0.
APOBEC3G (A3G), a member of cytidine deaminase family, has potent anti-human immunodeficiency virus type 1 (HIV-1) activity. It has been demonstrated that alpha interferon (IFN-alpha) can significantly enhance the expression of A3G in human primary resting CD4(+) T-cells, macrophages and primary hepatocytes, subsequently decreasing their viral susceptibility. Plasmacytoid dendritic cells (pDCs) are key effectors in innate host immunity, mediating adaptive immune responses and stimulating IFN-alpha production in reaction to various stimuli. In this report, we demonstrate that IFN-alpha, either exogenously added to- or endogenously secreted by pDCs, can enhance the expression of A3G and its family members such as A3A, A3C and A3F. We have also shown that IFN-alpha can inhibit HIV-1 expression in pDCs. This inhibitory effect could be countered by addition of an A3G-specific short interfering RNA, indicating that IFN-alpha-induced A3G plays a key role in mediating pDCs response to HIV-1. Given the central role played by pDCs in orchestrating the IFN-alpha/A3G intercellular network and intracellular signal pathway, our data indicate that pDCs themselves are also protected by an IFN-alpha/A3G-mediated innate immunity barrier from HIV-1 infection.
载脂蛋白B mRNA编辑酶催化多肽样蛋白3G（APOBEC3G，A3G）是胞苷脱氨酶家族的一员，具有强大的抗1型人类免疫缺陷病毒（HIV-1）活性。已证明，α干扰素（IFN-α）可显著增强A3G在人原代静息CD4(+)T细胞、巨噬细胞和原代肝细胞中的表达，进而降低它们对病毒的易感性。浆细胞样树突状细胞（pDC）是先天性宿主免疫中的关键效应细胞，介导适应性免疫反应，并在对各种刺激的反应中刺激IFN-α的产生。在本报告中，我们证明，无论是外源添加到pDC中的还是由pDC内源性分泌的IFN-α，均可增强A3G及其家族成员如A3A、A3C和A3F的表达。我们还表明，IFN-α可抑制pDC中HIV-1的表达。添加A3G特异性短干扰RNA可抵消这种抑制作用，表明IFN-α诱导的A3G在介导pDC对HIV-1的反应中起关键作用。鉴于pDC在协调IFN-α/A3G细胞间网络和细胞内信号通路中发挥的核心作用，我们的数据表明，pDC自身也受到IFN-α/A3G介导的先天性免疫屏障的保护，免受HIV-1感染。
