This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.02039-06v1 81/7/3339    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Surjit, M. Articles by Lal, S. K. Search for Related Content PubMed PubMed Citation Articles by Surjit, M. Articles by Lal, S. K.

Cytoplasmic Localization of the ORF2 Protein of Hepatitis E Virus Is Dependent on Its Ability To Undergo Retrotranslocation from the Endoplasmic Reticulum

Virology Group, International Centre for Genetic Engineering & Biotechnology, Aruna Asaf Ali Road, New Delhi 110067, India

Received 18 September 2006/ Accepted 7 January 2007

Hepatitis E virus (HEV) is a positive-strand RNA virus that is prevalent in much of the developing world. ORF2 is the major capsid protein of HEV. Although ORF2 is an N-linked glycoprotein, it is abundantly located in the cytoplasm in addition to having membrane and surface localization. The mechanism by which ORF2 protein obtains access to the cytoplasm is unknown. In this report, we prove that initially all ORF2 protein is present in the endoplasmic reticulum and a fraction of it becomes retrotranslocated to the cytoplasm. The ability of ORF2 to be retrotranslocated is dependent on its glycosylation status and follows the canonical dislocation pathway. However, in contrast to general substrates of the dislocation pathway, retrotranslocated ORF2 protein is not a substrate of the 26S proteasome complex and is readily detectable in the cytoplasm in the absence of any protease inhibitor, suggesting that the retrotranslocated protein is stable in the cytoplasm. This study thus defines the pathway by which ORF2 obtains access to the cytoplasm.

Published ahead of print on 17 January 2007.

This article has been cited by other articles:

• Graff, J., Zhou, Y.-H., Torian, U., Nguyen, H., St. Claire, M., Yu, C., Purcell, R. H., Emerson, S. U. (2008). Mutations within Potential Glycosylation Sites in the Capsid Protein of Hepatitis E Virus Prevent the Formation of Infectious Virus Particles. J. Virol. 82: 1185-1194 [Abstract] [Full Text]