Journal article
The role of the downstream signal sequences in the maturation of the HBV middle surface glycoprotein: Development of a novel therapeutic vaccine candidate
Virology (New York, N.Y.), v 365(1)
2007
PMID: 17462693
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The signal sequences that mediate entry of the hepatitis B virus (HBV) envelope proteins into the endoplasmic reticulum (ER) are located within the S domain at positions 11–32 and at positions 80–98 (from the start of the S domain). In addition, hydrophobic patches at positions 160–184 and 189–210 of the S domain may also be involved in entry into the ER. The role of each of these domains in the entry of the HBV M glycoprotein into the ER was studied by deletion mutations of each of the signal sequences. Glycosylation of proteins was used as a marker of entry into the ER. Our results indicate that association with the ER could not be prevented by the deletion of either individual or combinations of the HBV signal sequences. M protein lacking signal sequence I was able to enter the ER and had limited secretion. In contrast, M protein lacking signal sequence II could not be secreted but still entered the ER. M protein lacking signal sequences I and II, while still associated with the ER, was rapidly degraded by the cytosolic proteasome. The potential use of such a vector as a CTL vaccine was tested through an
in vitro antigen presentation assay. In this assay, a DNA vaccine candidate lacking signal sequences I and II lead to a >
6-fold increase in CTL activation, as compared to the vector expressing wild type M protein. These results suggest that increased degradation of the HBV envelope proteins can lead to enhanced antigen presentation.
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Details
- Title
- The role of the downstream signal sequences in the maturation of the HBV middle surface glycoprotein: Development of a novel therapeutic vaccine candidate
- Creators
- Yuanjie Liu - Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA 18902, USAEnder Simsek - Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA 18902, USAPamela Norton - Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA 18902, USAGomathinayagam Sinnathamby - Institute for Hepatitis and Virus Research, Doylestown, PA 18902, USARamila Philip - Institute for Hepatitis and Virus Research, Doylestown, PA 18902, USATimothy Block - Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA 18902, USATianlun Zhou - Institute for Hepatitis and Virus Research, Doylestown, PA 18902, USAAnand Mehta - Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA 18902, USA
- Publication Details
- Virology (New York, N.Y.), v 365(1)
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000247584900002
- Scopus ID
- 2-s2.0-34250194001
- Other Identifier
- 991014877803304721
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- Web of Science research areas
- Virology