Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
J Virol. 2013 Jun;87(11):6073-80. doi: 10.1128/JVI.00579-12. Epub 2013 Mar 27.
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.
APOBEC3 蛋白在逆转录过程中使逆转录病毒基因组发生高度突变，从而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) 和猴免疫缺陷病毒 (SIV) 已经进化出 Vif 蛋白，该蛋白将 APOBEC3 蛋白靶向蛋白酶体降解。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 蛋白破坏是否会导致在慢病毒感染细胞的表面上产生和呈现 APOBEC3 衍生的 T 细胞表位尚不清楚。在这里，我们使用源自多种 Vif 敏感的 APOBEC3 蛋白的肽，在 HIV-1 感染的患者和 SIV 感染的恒河猴中鉴定出 APOBEC3 特异性 T 细胞反应。这些结果提出了这些 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的可能性。
