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.
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.
Simsek
Ender
E
Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University College of Medicine, Philadelphia, Pennsylvania, USA.
Mehta
Anand
A
Zhou
Tianlun
T
Dwek
Raymond A
RA
Block
Timothy
T
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015686:Gene Products, env / Q000378:metabolism*; D005959:Glucosidases / Q000037:antagonists & inhibitors; D006515:Hepatitis B virus / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D014779:Virus Replication
D015853:Cysteine Proteinase Inhibitors; D015686:Gene Products, env; D009842:Oligopeptides; C067713:lactacystin; D005959:Glucosidases; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine; C078846:epoxomicin