Kaposi’s Sarcoma-Associated Herpesvirus K3 and K5 Proteins Down Regulate Both DC-SIGN and DC-SIGNR

摘要: Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of multicentric Castleman’s disease, primary effusion lymphoma and sarcoma. In this study, we show that like C-type lectin DC-SIGN, closely related DC-SIGNR can also enhance KSHV infection. Following infection, they are both targeted for down modulation our data indicate MARCH-family ubiquitin ligase K5 mediating regulation subsequent targeting degradation DC-SIGN in context virus. The viral K3 protein, able to target these lectins exogenous expressions studies, but only weakly during addition requiring a functional RING-CH domain, several protein trafficking motifs C-terminal region important DC-SIGNR. Further exploration revealed endocytosed from cell surface THP-1 monocytes, degraded an internal location with minimal endocytosis HEK-293 cells. Pull-down preferentially associate immature forms lectins, their ubiquitylation degradation. Together, emphasize molecular complexities K5, while expanding repertoire targets two proteins.