Characterization of the HHV-6B U20 Immunoevasin.
Characterization of the HHV-6B U20 Immunoevasin.
复制标题
HHV-6B U20 免疫evasin 的表征。
DOI：
10.1128/jvi.01890-22
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发表时间：
2023
影响因子：
5.4
通讯作者：
Hudson,AmyW
中科院分区：
文献类型：
--
作者：
Schneider,ChristineL;Whyte,MelissaL;Konrad,SherylL;Hudson,AmyW
玫瑰花状病毒（人类疱疹病毒6A [HHV-6A]，-6B和-7）在幼儿期感染>90%的人群，并被认为在宿主的整个生命中保持潜伏或持续。因此，这些病毒是所有病毒中最普遍和最隐蔽的病毒之一;它们必须在宿主的整个生命周期中逃脱免疫检测，然而，人们对这些病毒如何成功地逃脱宿主防御知之甚少。在这里，我们的特点的表达，贩运，和翻译后修饰的HHV 6 B U20基因产物，这是在一个独特的基因块的玫瑰病毒编码。HHV-6 B U20通过分泌系统缓慢运输，对其N-连接聚糖进行几次翻译后修饰，指示表面表达的糖蛋白，并最终在被内化之前到达细胞表面。有趣的是，U20也在至少一个Ser、Thr或Tyr残基上磷酸化。这些结果提供了一个框架，以了解U20的作用（S）在逃避宿主defenses.IMPORTANCEThe玫瑰病毒U20蛋白是病毒编码的整合膜糖蛋白，具有I类主要组织相容性复合体（MHC）样折叠。令人惊讶的是，虽然来自HHV-6A和-6B的U20蛋白具有92%的同一性，但最近的研究将不同的功能归因于HHV 6A U20和HHV 6 B U20。HHV 6A U20被证明下调NKG 2D配体，而HHV 6 B U20被证明在HHV 6 B的非生产性感染期间抑制肿瘤坏死因子α（TNF-α）诱导的细胞凋亡（E. Kofod-Olsen，K. Ross-Hansen，M. H. Schleimann，D. K.詹森等人，J Virol 86：11483-11492，2012，https：//doi.org/10.1128/jvi.00847-12; A. E. Chaouat，B. Seliger，O. Mandelboim，D. Schmiedel，Front Immunol 12：714799，2021，https：//doi.org/10.3389/fimmu.2021.714799）。在这里，我们进行了细胞生物学和生物化学表征的贩运，糖基化，和翻译后修饰发生在HHV 6 B U20。
Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) infect >90% of the human population during early childhood and are thought to remain latent or persistent throughout the life of the host. As such, these viruses are among the most pervasive and stealthy of all viruses; they must necessarily excel at escaping immune detection throughout the life of the host, and yet, very little is known about how these viruses so successfully escape host defenses. Here, we characterize the expression, trafficking, and posttranslational modifications of the HHV6B U20 gene product, which is encoded within a block of genes unique to the roseoloviruses. HHV-6B U20 trafficked slowly through the secretory system, receiving several posttranslational modifications to its N-linked glycans, indicative of surface-expressed glycoproteins, and eventually reaching the cell surface before being internalized. Interestingly, U20 is also phosphorylated on at least one Ser, Thr, or Tyr residue. These results provide a framework to understand the role(s) of U20 in evading host defenses.IMPORTANCEThe roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. Surprisingly, although U20 proteins from HHV-6A and -6B share 92% identity, recent studies ascribe different functions to HHV6A U20 and HHV6B U20. HHV6A U20 was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483–11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799). Here, we have performed cell biological and biochemical characterization of the trafficking, glycosylation, and posttranslational modifications occurring on HHV6B U20.