Large hepatitis delta antigen is a novel clathrin adaptor-like protein.
Clathrin-mediated endocytosis is a common pathway for viral entry, but little is known about the direct association of viral protein with clathrin in the cytoplasm. In this study, a putative clathrin box known to be conserved in clathrin adaptors was identified at the C terminus of the large hepatitis delta antigen (HDAg-L). Similar to clathrin adaptors, HDAg-L directly interacted with the N terminus of the clathrin heavy chain through the clathrin box. HDAg-L is a nucleocytoplasmic shuttle protein important for the assembly of hepatitis delta virus (HDV). Here, we demonstrated that brefeldin A and wortmannin, inhibitors of clathrin-mediated exocytosis and endosomal trafficking, respectively, specifically blocked HDV assembly but had no effect on the assembly of the small surface antigen of hepatitis B virus. In addition, cytoplasm-localized HDAg-L inhibited the clathrin-mediated endocytosis of transferrin and the degradation of epidermal growth factor receptor. These results indicate that HDAg-L is a new clathrin adaptor-like protein, and it may be involved in the maturation and pathogenesis of HDV coinfection or superinfection with hepatitis B virus through interaction with clathrin.
Huang
Cheng
C
Institute of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, No. 1, Jen-Ai Road, First Section, Taipei, Taiwan.
Chang
Shin C
SC
Yu
I-Chen
IC
Tsay
Yeou-Guang
YG
Chang
Ming-Fu
MF
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D033922:Clathrin Heavy Chains / Q000737:chemistry* / Q000378:metabolism; D003698:Hepatitis Delta Virus / Q000737:chemistry* / Q000378:metabolism; D035923:Hepatitis delta Antigens / Q000737:chemistry* / Q000378:metabolism; D006801:Humans
D035923:Hepatitis delta Antigens; C442244:hepatitis delta virus large antigen; D033922:Clathrin Heavy Chains