The large GTPase dynamin is required for hepatitis B virus protein secretion from hepatocytes

Ahmad S. Abdulkarim, Hong Cao, Bing Huang, Mark A. McNiven

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Background/Aims: The hepatocellular transport pathways and cellular proteins utilized during the packaging and secretion of hepatitis B virus are poorly understood. In this study, we tested if the large GTPase dynamin, a protein involved in vesicle formation and secretion at the trans-Golgi network in hepatocytes, is also used by hepatitis B virus (HBV) in secreting viral proteins. Methods: Using HepG2.2.15 cells expressing the full-length HBV genome, we tested the effects of wild-type and mutant dynamin on the localization and secretion of two hepatitis B antigens, hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Distribution of these two antigens was analyzed morphologically in cells transiently transfected with wild-type or mutant dynamin constructs, whereas secretion of the antigens was measured by testing for antigen levels in the media of transfected cells. Results: Mutant dynamin was found to induce a striking redistribution of HBsAg and HBeAg to a perinuclear compartment, as well as a decrease in the levels of HBsAg and HBeAg present in cell culture media indicating a reduction in viral protein secretion. At the electron microscopy level, cells expressing the mutant dynamin showed a marked accumulation of viral particles in dilated cisternae of an uncharacterized cellular compartment. Conclusions: Intact dynamin function is required for secretion of HBV proteins from hepatocytes through an uncharacterized cellular compartment.

Original languageEnglish (US)
Pages (from-to)76-83
Number of pages8
JournalJournal of hepatology
Volume38
Issue number1
DOIs
StatePublished - Jan 1 2003

Keywords

  • Dynamin
  • Hepatitis B
  • Hepatitis B virus
  • Viral protein
  • Viral secretion

ASJC Scopus subject areas

  • Hepatology

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