Inhibition of MHC class I-restricted antigen presentation by γ2-herpesviruses
Inhibition of MHC class I-restricted antigen presentation by γ2-herpesviruses
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DOI：
10.1073/pnas.150240097
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发表时间：
2000-07-18
影响因子：
11.1
通讯作者：
Lehner, PJ
中科院分区：
文献类型：
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作者：
Stevenson, PG;Efstathiou, S;Lehner, PJ
γ-疱疹病毒，与α-和β-疱疹病毒相反。在裂解周期复制过程中，不知道是否抑制抗原呈递给CD 8（+）细胞毒性T淋巴细胞（CTL）。然而，鼠γ-疱疹病毒68在CD 4（+）T细胞缺陷小鼠中引起慢性溶解性感染，尽管持续存在大量的CTL应答，这表明发生了CTL逃避。在这里，我们表明，与宿主蛋白质合成关闭不同，γ-疱疹病毒68下调表面MHC I类在裂解感染的成纤维细胞上的表达，并抑制其识别抗原特异性CTL，病毒K3基因，编码含锌指蛋白。显著降低新生I类分子的半衰期和表面MHC I类表达水平，并且其本身足以阻断抗原呈递。相关卡波西肉瘤相关病毒的同源K3和Ks基因也抑制抗原呈递并降低细胞表面HLA I类抗原的表达。因此，似乎至少两种γ-疱疹病毒共享的免疫逃避策略允许在面对强CTL免疫时继续裂解感染。
The gamma-herpesviruses, in contrast to the alpha- and beta-herpesviruses. are not known to inhibit antigen presentation to CD8(+) cytotoxic T lymphocytes (CTLs) during lytic cycle replication. However, murine gamma-herpesvirus 68 causes a chronic lytic infection in CD4(+) T cell-deficient mice despite the persistence of a substantial CTL response, suggesting that CTL evasion occurs. Here we show that, distinct from host protein synthesis shutoff, gamma-herpesvirus 68 down-regulates surface MHC class I expression on lytically infected fibroblasts and inhibits their recognition by antigen-specific CTLs, The viral K3 gene, encoding a zinc-finger-containing protein. dramatically reduced the half-life of nascent class I molecules and the level of surface MHC class I expression and was by itself sufficient to block antigen presentation. The homologous K3 and Ks genes of the related Kaposi's sarcoma-associated virus also inhibited antigen presentation and decreased cell surface expression of HLA class I antigens. Thus it appears that an immune evasion strategy shared by at least two gamma-herpesviruses allows continued lytic infection in the face of strong CTL immunity.