Molluscum contagiosum virus (MCV) is a common cause of benign skin lesions in young children and currently the only endemic human poxvirus. Following the infection of primary keratinocytes in the epidermis, MCV induces the proliferation of infected cells and this results in the production of wart-like growths. Full productive infection is observed only after the infected cells differentiate. During this prolonged replication cycle the virus must avoid elimination by the host immune system. We therefore sought to investigate the function of the two major histocompatibility complex class-I-related genes encoded by the MCV genes mc033 and mc080. Following insertion into a replication-deficient adenovirus vector, codon-optimized versions of mc033 and mc080 were expressed as endoglycosidase-sensitive glycoproteins that localized primarily in the endoplasmic reticulum. MC080, but not MC033, downregulated cell-surface expression of endogenous classical human leucocyte antigen (HLA) class I and non-classical HLA-E by a transporter associated with antigen processing (TAP)-independent mechanism. MC080 exhibited a capacity to inhibit or activate NK cells in autologous assays in a donor-specific manner. MC080 consistently inhibited antigen-specific T cells being activated by peptide-pulsed targets. We therefore propose that MC080 acts to promote evasion of HLA-I-restricted cytotoxic T cells.

中文翻译：

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传染性软疣病毒 mc080 下调 HLA-I 会影响 NK 细胞识别并促进 CD8+ T 细胞逃避。


传染性软疣病毒（MCV）是幼儿良性皮肤病变的常见原因，也是目前唯一的地方性人类痘病毒。感染表皮中的初级角质形成细胞后，MCV 会诱导受感染细胞增殖，从而导致疣状生长的产生。仅在受感染细胞分化后才能观察到完全有效的感染。在这个漫长的复制周期中，病毒必须避免被宿主免疫系统消灭。因此，我们试图研究由 MCV 基因 mc033 和 mc080 编码的两个主要组织相容性复合物 I 类相关基因的功能。插入复制缺陷型腺病毒载体后，密码子优化版本的 mc033 和 mc080 表达为糖苷内切酶敏感的糖蛋白，主要定位于内质网。 MC080（而非 MC033）通过与抗原加工 (TAP) 无关的机制相关的转运蛋白下调内源性经典人类白细胞抗原 (HLA) I 类和非经典 HLA-E 的细胞表面表达。 MC080 在自体检测中以供体特异性方式表现出抑制或激活 NK 细胞的能力。 MC080 持续抑制肽脉冲靶标激活的抗原特异性 T 细胞。因此，我们认为 MC080 可以促进 HLA-I 限制性细胞毒性 T 细胞的逃避。