Functional analysis of the human cytomegalovirus immune evasion protein, pUS3(22kDa).
Functional analysis of the human cytomegalovirus immune evasion protein, pUS3(22kDa).
复制标题
人巨细胞病毒免疫逃避蛋白 pUS3(22kDa) 的功能分析。
DOI：
10.1016/s0042-6822(03)00545-2
复制
发表时间：
2003
期刊：
影响因子：
3.7
通讯作者：
Biegalke,BonitaJ
中科院分区：
文献类型：
--
作者：
Zhao,Yiqiang;Biegalke,BonitaJ
人巨细胞病毒（HCMV）是一种重要的机会致病菌，在免疫系统成熟的个体中很少引起疾病。HCMV US 3基因编码一种22 kDa的蛋白质，该蛋白质干扰病毒感染细胞的免疫识别。22-kDa US 3蛋白与主要组织相容性复合体（MHC）I类复合体结合，将其保留在内质网（ER）中，从而减少病毒抗原向细胞毒性T细胞的提呈。我们的研究表明，正确折叠的ER内腔域的US 3蛋白是必不可少的，但不足以与MHC I类复合物的相互作用。我们证明了22 kDa的US 3蛋白的跨膜结构域的要求，确认了其他人的结果，也表明，胞质羧基末端尾巴影响蛋白质的功能。US 3蛋白质的ER-内腔免疫球蛋白样折叠到内质网膜上对于MHC I类复合物的结合和保留至关重要。
Human cytomegalovirus (HCMV) is an important opportunistic pathogen that infrequently causes disease in individuals with mature immune systems. The HCMV US3 gene encodes a 22-kDa protein that interferes with immune recognition of virally infected cells. The 22-kDa US3 protein binds to major histocompatibility complex (MHC) class I complexes, retaining them in the endoplasmic reticulum (ER), thereby decreasing the presentation of viral antigen to cytotoxic T cells. Our studies demonstrate that correct folding of the ER lumenal domain of the US3 protein is essential, but insufficient for interactions with MHC class I complexes. We demonstrate a requirement for the transmembrane domain of the 22-kDa US3 protein, confirming the results of others, and also show that the cytosolic carboxyl-terminal tail influences the function of the protein. Anchoring of the ER-lumenal immunoglobulin-like fold of the US3 protein to the membrane of the endoplasmic reticulum is critical for the binding and retention of MHC class I complexes.