The HCMV gene products US11 and US2 differ in their ability to attack allelic forms of murine major histocompatibility complex (MHC) class I heavy chains.

The HCMV gene products US11 and US2 differ in their ability to attack allelic forms of murine major histocompatibility complex (MHC) class I heavy chains.
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HCMV基因产品US11和US2在攻击鼠类主要组织相容性复合物(MHC)I类重链的等位基因形式的能力方面有所不同。

DOI:
10.1084/jem.185.2.363
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发表时间:
1997-01-20
影响因子:
15.3
通讯作者:
Ploegh, H L
Ploegh, H L
中科院分区:
医学1区
文献类型:
--
作者:
Machold, R P;Wiertz, E J;Jones, T R;Ploegh, H L

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人巨细胞病毒通过加速破坏新合成的 I 类重链来下调人 I 类主要组织相容性复合体 (MHC) 分子的表达。 HCMV基因组包含至少两个基因,US11和US2,每个基因编码足以引起新合成的I类重链从内质网腔错位至胞质溶胶的产物。根据对小鼠 I 类分子 H-2Kb、Kd、Db、Dd 和 Ld 的降解能力的比较,US11 和 US2 基因产物对 I 类分子具有不同的特异性。具体来说,在转染US11基因的人星形细胞瘤细胞(U373-MG)中,重组牛痘病毒表达的Kb、Db、Dd和Ld分子迅速降解,而在US2转染的细胞中,只有Db和Dd明显不稳定。干扰 I 类限制表达的 HCMV 编码功能的多样性可能是响应 MHC 的多态性而进化的。
Human cytomegalovirus downregulates the expression of human class I major histocompatibility complex (MHC) molecules by accelerating destruction of newly synthesized class I heavy chains. The HCMV genome contains at least two genes, US11 and US2, each of which encode a product sufficient for causing the dislocation of newly synthesized class I heavy chains from the lumen of the endoplasmic reticulum to the cytosol. Based on a comparison of their abilities to degrade the murine class I molecules H-2Kb, Kd, Db, Dd, and Ld, the US11 and US2 gene products have non-identical specificities for class I molecules. Specifically, in human astrocytoma cells (U373-MG) transfected with the US11 gene, the Kb, Db, Dd, and Ld molecules expressed via recombinant vaccinia virus are rapidly degraded, whereas in US2-transfected cells, only Db and Dd are significantly destabilized. The diversity in HCMV-encoded functions that interfere with class I–restricted presentation likely evolved in response to the polymorphism of the MHC.