Defining APOBEC3 Expression Patterns in Human Tissues and Hematopoietic Cell Subsets
Defining APOBEC3 Expression Patterns in Human Tissues and Hematopoietic Cell Subsets
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DOI：
10.1128/jvi.01089-09
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发表时间：
2009-09-15
影响因子：
5.4
通讯作者：
Malim, Michael H.
中科院分区：
文献类型：
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作者：
Koning, Fransje A.;Newman, Edmund N. C.;Malim, Michael H.
人类APOBEC3酶是细胞DNA胞苷脱氨酶，可抑制和/或使多种逆转录病毒、反转录转座子和DNA病毒发生突变。在这里，我们报告了人类APOBEC3基因表达的详细检查，重点是APOBEC3G （A3G）和APOBEC3F (A3F)，它们是人类免疫缺陷病毒1型（HIV-1）感染的有效抑制剂，但被HIV-1 Vif抑制。A3G和A3F在造血细胞群中广泛表达，包括T细胞、B细胞和髓细胞，以及mRNA水平与淋巴样细胞含量广泛相关的组织中（性腺组织除外）。通过测量mRNA拷贝数，我们发现A3G mRNA的丰度是A3F mRNA的10倍左右，这意味着A3G是体内更重要的抗hiv -1因子。A3G和A3F水平在供体之间也存在差异，这些差异持续12个月以上。对T细胞活化或细胞因子的反应表明，α干扰素（ifn - α）诱导巨噬细胞和树突状细胞（DCs）的A3G和A3F mRNA水平是α干扰素（ifn - α）的10倍，而初始CD4(+) T细胞的A3G和A3F mRNA水平是α干扰素的4倍。然而，免疫印迹显示，巨噬细胞和dc中A3G蛋白水平可被ifn - α诱导，而T细胞中不受ifn - α的影响。相比之下，t细胞活化和ifn - γ对A3G或A3F表达的影响很小。最后，我们注意到在CD4(+) T细胞、巨噬细胞和dc中，A3A mRNA表达和蛋白表达对ifn - α诱导非常敏感，但对T细胞活化或其他细胞因子不敏感。鉴于A3A不影响HIV-1感染，这些观察结果暗示该蛋白可能参与早期抗病毒先天免疫反应。
Human APOBEC3 enzymes are cellular DNA cytidine deaminases that inhibit and/or mutate a variety of retroviruses, retrotransposons, and DNA viruses. Here, we report a detailed examination of human APOBEC3 gene expression, focusing on APOBEC3G (A3G) and APOBEC3F (A3F), which are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) infection but are suppressed by HIV-1 Vif.A3G and A3F are expressed widely in hematopoietic cell populations, including T cells, B cells, and myeloid cells, as well as in tissues where mRNA levels broadly correlate with the lymphoid cell content (gonadal tissues are exceptions). By measuring mRNA copy numbers, we find that A3G mRNA is similar to 10-fold more abundant than A3F mRNA, implying that A3G is the more significant anti-HIV-1 factor in vivo. A3G and A3F levels also vary between donors, and these differences are sustained over 12 months. Responses to T-cell activation or cytokines reveal that A3G and A3F mRNA levels are induced similar to 10-fold in macrophages and dendritic cells (DCs) by alpha interferon (IFN-alpha) and similar to 4-fold in naive CD4(+) T cells. However, immunoblotting revealed that A3G protein levels are induced by IFN-alpha in macrophages and DCs but not in T cells. In contrast, T-cell activation and IFN-gamma had a minimal impact on A3G or A3F expression. Finally, we noted that A3A mRNA expression and protein expression are exquisitely sensitive to IFN-alpha induction in CD4(+) T cells, macrophages, and DCs but not to T-cell activation or other cytokines. Given that A3A does not affect HIV-1 infection, these observations imply that this protein may participate in early antiviral innate immune responses.