Tat-enhanced delivery of the C terminus of HDAg-L inhibits assembly and secretion of hepatitis D virus

Hsiu Chen Huang, Hsu Feng Lu, Yu Heng Lai, Chung Pei Lee, Hui Kang Liu, Cheng Huang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Hepatitis D virus (HDV) contains a single-stranded circular RNA genome that encodes two forms of hepatitis delta antigen (HDAg), the small delta antigen (HDAg-S) and the large delta antigen (HDAg-L). The two proteins have an identical amino acid sequence, except that HDAg-L has a 19-amino-acid extension at the C terminus. The domain spanning amino acid residues 198-210 of the HDAg-L (HDAg-L(198-210)) contains a nuclear export signal (NES), which is important for the nuclear export of HDV ribonucleoprotein to the cytoplasm. In this study, we established a cell permeable TAT-HA-HDAg-L(198-210) fusion protein using an E. coli protein expression system, to determine its function during HDV infection. The cytotoxicity of the TAT-HA-HDAg-L(198-210) fusion protein was investigated using an MTT assay, while a GST pull-down assay revealed that the TAT-HA-HDAg-L(198-210) fusion protein interfered with the interaction between HDAg-L and clathrin heavy chain (CHC). In addition, the cellular distribution of HDAg-L, in the presence of HBsAg, was observed by immunofluorescence staining and the TAT-HA-HDAg-L(198-210) fusion protein was found to impede the nuclear export of HDAg-L. Furthermore, assembly of HDV virus-like particles (VLPs) was decreased by the expression of the TAT-HDAg-L(198-210) fusion protein. The TAT-HA-HDAg-L(198-210) fusion protein also inhibited virus particle assembly and HDV secretion in a mouse model. These results suggest that the TAT-HA-HDAg-L(198-210) fusion protein inhibits the nuclear export of HDAg-L and competes with the C terminus of HDAg-L for interaction with CHC, and may have potential as a therapeutic agent for HDV infection.

Original languageEnglish
Pages (from-to)69-78
Number of pages10
JournalAntiviral Research
Volume150
DOIs
StatePublished - Feb 2018

Keywords

  • HDV assembly
  • Hepatitis delta antigen
  • Tat-enhanced delivery

Fingerprint

Dive into the research topics of 'Tat-enhanced delivery of the C terminus of HDAg-L inhibits assembly and secretion of hepatitis D virus'. Together they form a unique fingerprint.

Cite this