TY - JOUR
T1 - The large GTPase dynamin is required for hepatitis B virus protein secretion from hepatocytes
AU - Abdulkarim, Ahmad S.
AU - Cao, Hong
AU - Huang, Bing
AU - McNiven, Mark A.
N1 - Funding Information:
We would like to thank H.M. Thompson and J.D. Orth for reviewing the manuscript. We also thank E.W. Kruger, B.J. Oswald and K.J. Simmons for technical support and preparation of the manuscript. A.S. Abdulkarim is supported by a grant from the American Liver Foundation (2001). M.A. McNiven is supported by a grant from the National Institutes of Health.
PY - 2003/1/1
Y1 - 2003/1/1
N2 - 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.
AB - 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.
KW - Dynamin
KW - Hepatitis B
KW - Hepatitis B virus
KW - Viral protein
KW - Viral secretion
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U2 - 10.1016/S0168-8278(02)00326-4
DO - 10.1016/S0168-8278(02)00326-4
M3 - Article
C2 - 12480563
AN - SCOPUS:0037230596
SN - 0168-8278
VL - 38
SP - 76
EP - 83
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 1
ER -