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Journal of Virology, June 2007, p. 5985-5994, Vol. 81, No. 11
0022-538X/07/$08.00+0 doi:10.1128/JVI.02809-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Institute of Biochemistry and Molecular Biology,1 Institute of Microbiology, National Taiwan University College of Medicine,2 Institute of Biochemistry and Molecular Biology, National Yang-Ming University School of Life Sciences, Taipei, Taiwan3
Received 20 December 2006/ Accepted 13 March 2007
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.
Published ahead of print on 21 March 2007.
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