Glucosidase inhibition enhances presentation of de-N-glycosylated hepatitis B virus epitopes by major histocompatibility complex class I in vitro and in woodchucks.

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Pamela A NortonTimothy M Block

Abstract

In this report, the possibility of pharmacologically altering the hepatitis B virus (HBV) epitopes presented by major histocompatibility complex class I on infected cells is demonstrated. The HBV middle envelope glycoprotein (MHBs) maturation appears to require calnexin-mediated folding. This interaction is dependent on glucosidases in the endoplasmic reticulum. Prevention of HBV envelope protein maturation in cultured cells through use of glucosidase inhibitors, such as 6-O-butanoyl castanospermine and N-nonyl deoxynorjirimycin, resulted in MHBs degradation by proteasomes. The de-N-glycosylation associated with polypeptide degradation was predicted to result in conversion of asparagine residues into aspartic acid residues. This prediction was confirmed by showing that peptides corresponding to the N-glycosylation sequons of MHBs, but with aspartic acid replacing asparagine, (1) can prime human cytotoxic T lymphocytes that recognize HBV-producing cells and (2) that the presentation of these envelope motifs by major histocompatibility complex class I is enhanced by incubation with glucosidase inhibitors. Moreover, although peripheral blood mononuclear cells isolated from woodchucks chronically infected with woodchuck hepatitis v...Continue Reading

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Citations

Feb 9, 2013·Antiviral Research·Timothy M BlockJu-Tao Guo
Feb 5, 2011·Nature Reviews. Gastroenterology & Hepatology·Sandra Ciesek, Michael P Manns
Aug 5, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·T Jake LiangAnna S Lok
Apr 2, 2013·Virology·Carolina TorresViviana Andrea Mbayed
Jun 27, 2015·Antiviral Research·Timothy M BlockCarol L Brosgart
Jan 9, 2020·Scientific Reports·Michiyo HayakawaYoshiki Murakami
May 18, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Meijuan ZhengZhigang Tian
Nov 1, 2013·Emerging Microbes & Infections·Jinhong ChangTimothy Block
Feb 16, 2021·The Journal of Pathology·Deniz KuscuogluPavel Strnad

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