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Journal article
A Ubiquitin Independent Degradation Pathway Utilized by a Hepatitis B Virus Envelope Protein to Limit Antigen Presentation
PloS one, v 6(9), pp e24477-e24477
28 Sep 2011
PMID: 21969857
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Hepatitis B virus envelope glycoproteins Large (L), Middle (M) and Small (S) are targets of the host cellular immune system. The extent to which the host recognizes viral antigens presented by infected cells is believed to play a decisive role in determining if an infection will be resolved or become chronic. As with other antigens, HBV envelope polypeptides must be degraded, presumably by cellular proteasomes, to be presented by the MHC I pathway. We have used M as a model to study this process and determine how ER quality control monitors these foreign polymeric proteins and disposes of them through the ER-associated degradation (ERAD) pathway. Using both wild type and mutant HBV M protein, we found that unlike most ERAD substrates, which require ubiquitination for retrotranslocation and degradation, the HBV M protein, which only contains two lysine residues, can undergo rapid and complete, ubiquitin independent, proteasome dependent degradation. The utilization of this pathway had a functional consequence, since proteins degraded through it, were poorly presented via MHC I. To test the hypothesis that the level of ubiquitination, independent of protein degradation, controls the level of antigen presentation, we inserted two additional lysines into both the wild type and mutant M protein. Amazingly, while the addition of the lysine residues dramatically increased the level of ubiquitination, it did not alter the rate of degradation. However and remarkably, the increased ubiquitination was associated with a dramatic increase in the level of antigen presentation. In conclusion, using the HBV surface protein as a model, we have identified a novel ubiquitin independent degradation pathway and determined that this pathway can have implications for antigen presentation and potentially viral pathogenesis.
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Details
- Title
- A Ubiquitin Independent Degradation Pathway Utilized by a Hepatitis B Virus Envelope Protein to Limit Antigen Presentation
- Creators
- Yuanjie Liu - Drexel UniversityJames S. Testa - Immunotope Inc., Doylestown, Pennsylvania, United States of AmericaRamila Philip - Immunotope (United States)Timothy M. Block - Drexel UniversityAnand S. Mehta - Drexel University
- Publication Details
- PloS one, v 6(9), pp e24477-e24477
- Publisher
- Public Library Science
- Number of pages
- 11
- Grant note
- U01AI054763 / National Institute of Allergy and Infectious Diseases (NIAID); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) UO1 CA084951-06 / NCI Early Research Detection Network (EDRN) U01CA084951 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01 CA120206-01 / National Cancer Institute (NCI); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) U01AI054763 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000295936900008
- Scopus ID
- 2-s2.0-80053288136
- Other Identifier
- 991019167720204721
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- Web of Science research areas
- Biochemistry & Molecular Biology