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Effects of hepatitis C virus envelope glycoprotein unfolded protein response activation on translation and transcription

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Abstract

The hepatitis C virus (HCV) envelope glycoproteins have been shown to cause ER stress and induce the unfolded protein response (UPR). Using a bicistronic reporter, we show that the envelope glycoproteins repressed both cap-dependent and HCV IRES-mediated translation in HeLa cells but displayed a differential repression of cap-dependent translation in Huh-7 cells. In contrast, the envelope glycoproteins repressed E2F transcriptional activity in both HeLa and Huh-7 cells and caused increased accumulation of the underphosphorylated retinoblastoma protein. Expression of the envelope glycoproteins induced eIF2α phosphorylation, suggesting a role of the UPR in regulating translation and E2F transcriptional activity. The envelope glycoproteins also enhanced transcriptional activity from the COX-2 promoter and endogenous COX-2 expression in HeLa cells, but not in Huh-7 cells. Together, these results suggest that the envelope glycoproteins may assume more functional roles in viral replication and host cell interactions.

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Acknowledgments

We thank Charlie Rice for the Huh-7 cell line, Jean Dubuisson for the anti-E1 and anti-E2 antibodies, Makoto Hijikata, Tatsuo Miyamura, Yoshiharu Matsuura, Richard Elliott, Martin Bennett and Thomas McIntyre for plasmids. This work was supported in part by a Medical Research Council Career Establishment grant G0000092 awarded to SWC. Microscopy was performed using a Zeiss epifluorescent microscope and a confocal microscope from a Biotechnology and Biological Sciences Research Council JREI equipment grant (JR00UMJAEQ, JR00UMJARC) to SWC.

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  1. Faculty of Life Sciences, The University of Manchester, 1.800 Stopford Building, Oxford Road, Manchester, M13 9PT, UK

    Shiu-Wan Chan & Philip Anthony Egan

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Correspondence to Shiu-Wan Chan.

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705_2009_495_MOESM1_ESM.ppt

Subcellular localization of E1 and E2 proteins. Fluorescent microscopy showing the subcellular localization of the ER-targeting E1 and E2 and the gfp-E1 and gfp-E2 devoid of signal peptides. Supplementary figure (PPT 1666 kb)

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Chan, SW., Egan, P.A. Effects of hepatitis C virus envelope glycoprotein unfolded protein response activation on translation and transcription. Arch Virol 154, 1631–1640 (2009). https://doi.org/10.1007/s00705-009-0495-5

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  • DOI: https://doi.org/10.1007/s00705-009-0495-5

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