APOBEC3A, APOBEC3B, and APOBEC3H Haplotype 2 Restrict Human T-Lymphotropic Virus Type 1
APOBEC3A, APOBEC3B, and APOBEC3H Haplotype 2 Restrict Human T-Lymphotropic Virus Type 1
复制标题
DOI：
10.1128/jvi.06570-11
复制
发表时间：
2012-06-01
影响因子：
5.4
通讯作者：
Muenk, Carsten
中科院分区：
文献类型：
--
作者：
Ooms, Marcel;Krikoni, Aikaterini;Muenk, Carsten
人类 APOBEC3 家族由七种胞苷脱氨酶（A3A 至 A3H）组成，其中一些对 HIV-1 和其他逆转录病毒表现出有效的抗逆转录病毒活性。分析 A3G 对人类 T 淋巴细胞病毒 1 型 (HTLV-1) 感染性影响的研究得出了相互矛盾的结果，而且我们对其他 A3 蛋白限制 HTLV-1 的了解仍然有限。由于HTLV-1与HIV非常相似，靶向CD4(+) T细胞，因此我们假设A3G以外的A3蛋白限制HTLV-1。所有七种人类 A3 蛋白均在 HTLV-1 报告基因和 HIV-1 感染性测定中进行了测试。我们发现 A3A、A3B 和 A3H 单倍型 2 (A3H hapII) 是 HTLV-1 的有效抑制剂。相比之下，野生型 HIV-1 受 A3B 和 A3H hapII 限制，但不受 A3A 限制。 A3A、A3B和A3H hapII的催化位点突变体表明A3A和A3B限制HTLV-1需要脱氨酶活性。然而，A3H hapII 在限制 HTLV-1 时以不依赖脱氨酶的方式发挥作用，而限制 HIV-1 则需要脱氨酶活性。我们还分析了从 HTLV-1 感染患者获得的 5 个 T 细胞系中 HTLV-1 的 A3 编辑。这些细胞系包含经过广泛编辑的 HTLV-1 序列，在二核苷酸环境中具有 G 至 A 突变，表明 APOBEC3 诱变。报告细胞和患者来源的细胞系的 A3 诱导突变的比较表明，A3G 以及其他 A3 成员（可能是 A3A 和 A3B）在体内影响 HTLV-1。综上所述，我们的数据表明 HTLV-1 可能是多种 A3 蛋白的靶标。
The human APOBEC3 family consists of seven cytidine deaminases (A3A to A3H), some of which display potent antiretroviral activity against HIV-1 and other retroviruses. Studies that analyzed the effect of A3G on human T-lymphotropic virus type 1 (HTLV-1) infectivity resulted in conflicting findings, and our knowledge of HTLV-1 restriction by other A3 proteins remains limited. Since HTLV-1, much like HIV, targets CD4(+) T cells, we hypothesized that A3 proteins other than A3G restrict HTLV-1. All seven human A3 proteins were tested in HTLV-1 reporter and HIV-1 infectivity assays. We show that A3A, A3B, and A3H haplotype 2 (A3H hapII) acted as potent inhibitors of HTLV-1. Wild-type HIV-1, in contrast, was restricted by A3B and A3H hapII, but not by A3A. Catalytic site mutants of A3A, A3B, and A3H hapII showed that A3A and A3B restriction of HTLV-1 required deaminase activity. However, A3H hapII acted in a deaminase-independent manner when restricting HTLV-1, while requiring deaminase activity for HIV-1 restriction. We also analyzed A3 editing of HTLV-1 in five T-cell lines obtained from HTLV-1-infected patients. These cell lines contained extensively edited HTLV-1 sequences with G-to-A mutations in dinucleotide contexts suggestive of APOBEC3 mutagenesis. Comparison of the A3-induced mutations from reporter cells and the patient-derived cell lines indicate that A3G but also other A3 members, possibly A3A and A3B, affect HTLV-1 in vivo. Taken together, our data indicate that HTLV-1 is a likely target for multiple A3 proteins.