Epstein-Barr Virus Isolates Retain Their Capacity To Evade T Cell Immunity through BNLF2a despite Extensive Sequence Variation

Epstein-Barr Virus Isolates Retain Their Capacity To Evade T Cell Immunity through BNLF2a despite Extensive Sequence Variation
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DOI:
10.1128/jvi.05151-11
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发表时间:
2012-01-01
影响因子:
5.4
通讯作者:
Wiertz, Emmanuel J. H. J.
Wiertz, Emmanuel J. H. J.
中科院分区:
医学2区
文献类型:
--
作者:
Horst, Danielle;Burrows, Scott R.;Wiertz, Emmanuel J. H. J.

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Epstein-Barr病毒(EBV)编码的免疫逃避蛋白BNLF2a抑制与抗原加工(TAP)相关的转运蛋白,从而下调细胞表面的HLA I类表达。结果,细胞毒性 T 细胞对 EBV 感染细胞的识别受到损害。在这里,我们表明在天然 EBV 分离株中观察到 BNLF2a 蛋白的序列多态性,并有正选择的证据。尽管存在这些突变,BNLF2a 变体仍能有效降低细胞表面 HLA I 类水平。 BNLF2a 功能在 EBV 进化过程中的保守性意味着病毒 TAP 抑制剂在病毒感染期间阻止 T 细胞识别方面发挥着重要作用。
The Epstein-Barr virus (EBV)-encoded immune evasion protein BNLF2a inhibits the transporter associated with antigen processing (TAP), thereby downregulating HLA class I expression at the cell surface. As a consequence, recognition of EBV-infected cells by cytotoxic T cells is impaired. Here, we show that sequence polymorphism of the BNLF2a protein is observed with natural EBV isolates, with evidence for positive selection. Despite these mutations, the BNLF2a variants efficiently reduce cell surface HLA class I levels. This conservation of BNLF2a function during evolution of EBV implies an important role for the viral TAP inhibitor in preventing T cell recognition during viral infection.