The antigen presentation molecule MR1 (major histocompatibility complex, class I–related) presents ligands derived from the riboflavin (vitamin B) synthesis pathway, which is not present in mammalian species or viruses, to mucosal-associated invariant T (MAIT) cells. In this study, we demonstrate that varicella zoster virus (VZV) profoundly suppresses MR1 expression. We show that VZV targets the intracellular reservoir of immature MR1 for degradation, while preexisting, ligand-bound cell surface MR1 is protected from such targeting, thereby highlighting an intricate temporal relationship between infection and ligand availability. We also identify VZV open reading frame (ORF) 66 as functioning to suppress MR1 expression when this viral protein is expressed during transient transfection, but this is not apparent during infection with a VZV mutant virus lacking ORF66 expression. This indicates that VZV is likely to encode multiple viral genes that target MR1. Overall, we identify an immunomodulatory function of VZV whereby infection suppresses the MR1 biosynthesis pathway.

中文翻译：

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水痘带状疱疹病毒损害非经典主要组织相容性复合体 I 类相关基因蛋白 (MR1) 的表达

抗原呈递分子 MR1（主要组织相容性复合物，I 类相关）将源自核黄素（维生素 B）合成途径的配体呈递给粘膜相关不变性 T (MAIT) 细胞，而核黄素（维生素 B）合成途径不存在于哺乳动物物种或病毒中。在这项研究中，我们证明水痘带状疱疹病毒 (VZV) 极大地抑制了 MR1 的表达。我们表明 VZV 靶向未成熟 MR1 的细胞内储库进行降解，而先前存在的配体结合细胞表面 MR1 受到保护免受此类靶向，从而突出了感染和配体可用性之间错综复杂的时间关系。我们还发现 VZV 开放阅读框 (ORF) 66 在瞬时转染期间表达该病毒蛋白时起到抑制 MR1 表达的作用，但这在感染缺乏 ORF66 表达的 VZV 突变病毒期间并不明显。这表明 VZV 可能编码多个靶向 MR1 的病毒基因。总体而言，我们确定了 VZV 的免疫调节功能，感染可抑制 MR1 生物合成途径。