Human cytomegalovirus (HCMV) is a globally ubiquitous pathogen and causes congenital infection as well as opportunistic infection in immunocompromised patients. The HCMV UL42 gene encodes a membrane protein that regulates the function of Nedd4 family ubiquitin E3 ligases through its PPxY motif. As HCMV envelope glycoprotein B (gB) also has a PPxY motif at its C-terminal cytoplasmic domain, we examined whether there was any relationship between UL42 protein and gB. Among the Nedd4 family proteins, Nedd4, Nedd4L, and Itch induced the degradation of gB in transiently expressing cells. The degradation of gB by Nedd4 was inhibited by proteasome inhibitor MG132, lysosome inhibitor chloroquine, and the co-expression of UL42 proteins. Among those Nedd4 family proteins, Itch was relocalized by the co-expression of gB to the perinuclear region of the cytoplasm. A co-immunoprecipitation assay demonstrated an interaction between gB and Itch through its PPxY motif. The 150 kDa gB precursor was aberrantly ubiquitinated, and the total amount of gB was quickly decreased in the absence of UL42. Our results indicate that UL42 prevents the degradation of gB by the inhibition of Nedd4 family proteins.

中文翻译：

---

人巨细胞病毒UL42蛋白通过抑制Nedd4家族泛素E3连接酶抑制糖蛋白B的降解

人类巨细胞病毒 (HCMV) 是一种全球普遍存在的病原体，在免疫功能低下的患者中会引起先天性感染和机会性感染。HCMV UL42基因编码一种膜蛋白，通过其 PPxY 基序调节 Nedd4 家族泛素 E3 连接酶的功能。由于 HCMV 包膜糖蛋白 B (gB) 在其 C 端细胞质结构域也具有 PPxY 基序，我们检查了 UL42 蛋白和 gB 之间是否存在任何关系。在 Nedd4 家族蛋白中，Nedd4、Nedd4L 和 Itch 在瞬时表达细胞中诱导 gB 降解。Nedd4 对 gB 的降解受到蛋白酶体抑制剂 MG132、溶酶体抑制剂氯喹和 UL42 蛋白的共表达的抑制。在那些 Nedd4 家族蛋白中，Itch 通过 gB 的共表达重新定位到细胞质的核周区域。共免疫沉淀测定通过其 PPxY 基序证明了 gB 和 Itch 之间的相互作用。150kDa gB 前体异常泛素化，在没有 UL42 的情况下，gB 的总量迅速下降。我们的结果表明，UL42 通过抑制 Nedd4 家族蛋白来防止 gB 的降解。