Abstract
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.