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Journal of Virology, October 2005, p. 12914-12920, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12914-12920.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Hepatitis B Virus Large and Middle Glycoproteins Are Degraded by a Proteasome Pathway in Glucosidase-Inhibited Cells but Not in Cells with Functional Glucosidase Enzyme

Ender Simsek,¹ Anand Mehta,^2* Tianlun Zhou,³ Raymond A. Dwek,⁴ and Timothy Block^2*

Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University College of Medicine, Philadelphia, Pennsylvania,¹ Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, Pennsylvania,² Institute for Hepatitis and Virus Research (The Pennsylvania Commonwealth Institute), Doylestown, Pennsylvania,³ Department of Biochemistry, University of Oxford, Oxford, United Kingdom⁴

Received 13 March 2005/ Accepted 26 July 2005

The secretion of hepatitis B virus (HBV) large (LHBs) and middle (MHBs) envelope polypeptides from tissue cultures requires proper protein folding and is prevented by inhibitors of the endoplasmic reticulum (ER) glucosidase. Using competitive inhibitors of the ER glucosidase, here it is shown that the amounts of glycosylated and unglycosylated forms of LHBs and MHBs proteins are all greatly reduced in tissue cultures producing HBV envelope glycoproteins. In contrast, the HBV small (SHBs) protein was not affected. The reduction in secretion of LHBs and MHBs proteins appears to be mediated by proteasomal degradation pathways, since it is prevented by either lactacystin or epoxomicin, two inhibitors of proteasomal degradation. Although there is no detectable proteasomal degradation of LHBs and MHBs in cells with functional glucosidase, the implications of the nearly quantitative sensitivity of glycosylated and unglycosylated forms of LHBs and MHBs proteins, with selective sparing of SHBs protein, in cells in which glucosidase is inhibited is surprising, and its implications are discussed.

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* Corresponding author. Mailing address for A. Mehta: Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA 18901. Phone: (215) 489-4905. Fax: (215) 489-4920. E-mail: anand.mehta{at}drexel.edu. Mailing address for T. Block: Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA 18901. Phone: (215) 489-4949. Fax: (215) 489-4921. E-mail: tim.block{at}drexel.edu.

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Journal of Virology, October 2005, p. 12914-12920, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12914-12920.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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