T Cells Target APOBEC3 Proteins in Human Immunodeficiency Virus Type 1-Infected Humans and Simian Immunodeficiency Virus-Infected Indian Rhesus Macaques
T Cells Target APOBEC3 Proteins in Human Immunodeficiency Virus Type 1-Infected Humans and Simian Immunodeficiency Virus-Infected Indian Rhesus Macaques
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DOI：
10.1128/jvi.00579-12
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发表时间：
2013-06-01
影响因子：
5.4
通讯作者：
Nixon, Douglas F.
中科院分区：
文献类型：
--
作者：
Champiat, Stephane;Garrison, Keith E.;Nixon, Douglas F.
APOBEC3蛋白通过在逆转录过程中使逆转录病毒基因组高度突变来介导强大的抗逆转录病毒活性。为了对抗APOBEC3并获得复制优势，慢病毒如人类免疫缺陷病毒1型(HIV-1)和猿猴免疫缺陷病毒(SIV)进化出Vif蛋白，该蛋白针对APOBEC3蛋白进行蛋白酶体降解。然而，蛋白酶体在T细胞肽表位的产生中起着关键作用。Vif介导的APOBEC3蛋白的破坏是否导致慢病毒感染细胞表面APOBEC3衍生的T细胞表位的产生和呈递尚不清楚。在这里，我们使用来自多种Vif敏感的APOBEC3蛋白的多肽，在HIV-1感染患者和SIV感染的恒河猴中识别APOBEC3特异性T细胞反应。这些结果提出了这样的可能性，即这些T细胞反应可能是更大的抗逆转录病毒免疫反应的一部分。
APOBEC3 proteins mediate potent antiretroviral activity by hypermutating the retroviral genome during reverse transcription. To counteract APOBEC3 and gain a replicative advantage, lentiviruses such as human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) have evolved the Vif protein, which targets APOBEC3 proteins for proteasomal degradation. However, the proteasome plays a critical role in the generation of T cell peptide epitopes. Whether Vif-mediated destruction of APOBEC3 proteins leads to the generation and presentation of APOBEC3-derived T cell epitopes on the surfaces of lentivirus-infected cells remains unknown. Here, using peptides derived from multiple Vif-sensitive APOBEC3 proteins, we identified APOBEC3-specific T cell responses in both HIV-1-infected patients and SIV-infected rhesus macaques. These results raise the possibility that these T cell responses may be part of the larger antiretroviral immune response.