Varicella-zoster virus retains major histocompatibility complex class I proteins in the Golgi compartment of infected cells
Varicella-zoster virus retains major histocompatibility complex class I proteins in the Golgi compartment of infected cells
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DOI：
10.1128/jvi.75.10.4878-4888.2001
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发表时间：
2001-05-01
影响因子：
5.4
通讯作者：
Arvin, AM
中科院分区：
文献类型：
--
作者：
Abendroth, A;Lin, I;Arvin, AM
我们试图研究水痘-带状疱疹病毒（VZV）感染对人成纤维细胞和T淋巴细胞表达主要组织相容性复合物I类（MHC I）分子的影响。流式细胞仪检测表明，VZV感染可显著降低成纤维细胞表面MHCI类分子的表达，但对转铁蛋白受体的表达无明显影响。重要的是，当人胎儿胸腺/肝移植物在SCID-hu小鼠中接种VZV时，细胞表面MHC I表达在VZV感染的人CD 3（+）T淋巴细胞上特异性下调，这是维持VZV病毒血症的主要靶点。在存在内切糖苷酶H的情况下，在脉冲追踪和免疫沉淀实验中检查了成纤维细胞中被VZV破坏的MHC I组装过程的阶段。MNC I复合物继续在VZV感染的细胞中组装，并且不保留在内质网中。相反，免疫荧光和共聚焦显微镜显示，VZV感染导致MHC I分子聚集，其共定位于高尔基体。晚期病毒基因表达的抑制感染的成纤维细胞与膦酰基乙酸的治疗没有影响调制的MHC I的表达，也没有转染的细胞表达立即早期病毒蛋白的质粒。然而，用携带早期基因ORF 66的质粒转染的细胞确实导致MHC I表达的显著下调，这表明该基因编码具有免疫调节功能的蛋白。因此，VZV通过削弱MHC I分子从高尔基体区室到细胞表面的转运来下调MHC I表达;这种作用可能使病毒在VZV发病过程中，包括T淋巴细胞相关病毒血症的关键阶段，逃避CD 8（+）T细胞免疫识别。
We sought to examine the effects of varicella-zoster virus (VZV) infection on the expression of major histocompatibility complex class I (MHC I) molecules by human fibroblasts and T lymphocytes. By flow cytometry, VZV infection reduced the cell surface expression of MHC I molecules on fibroblasts significantly, yet the expression of transferrin receptor was not affected. Importantly, when human fetal thymus/liver implants in SCID-hu mice were inoculated with VZV, cell surface MHC I expression was downregulated specifically on VZV-infected human CD3(+) T lymphocytes, a prominent target that sustains VZV viremia, The stage in the MHC I assembly process that was disrupted by VZV in fibroblasts was examined in pulse-chase and immunoprecipitation experiments in the presence of endoglycosidase H. MNC I complexes continued to be assembled in VZV-infected cells and were not retained in the endoplasmic reticulum, In contrast, immunofluorescence and confocal microscopy showed that VZV infection resulted in an accumulation of MHC I molecules which colocalized to the Golgi compartment. Inhibition of late viral gene expression by treatment of infected fibroblasts with phosphonoacetic acid did not influence the modulation of MHC I expression, nor did transfection of cells with plasmids expressing immediate early viral proteins. However, cells transfected with a plasmid carrying the early gene ORF66 did result in a significant downregulation of MHC I expression, suggesting that this gene encodes a protein with an immunomodulatory function, Thus, VZV downregulates MHC I expression by impairing the transport of MHC I molecules from the Golgi compartment to the cell surface; this effect may enable the virus to evade CD8(+) T-cell immune recognition during VZV pathogenesis, including the critical phase of T-lymphocyte-associated viremia.