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Herpes simplex virus-1 disarms the unfolded protein response in the early stages of infection

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Cell Stress and Chaperones Aims and scope

Abstract

Accumulation of mis- and unfolded proteins during viral replication can cause stress in the endoplasmic reticulum (ER) and trigger the unfolded protein response (UPR). If unchecked, this process may induce cellular changes detrimental to viral replication. In the report, we investigated the impact of HSV-1 on the UPR during lytic replication. We found that HSV-1 effectively disarms the UPR in early stages of viral infection. Only ATF6 activation was detected during early infection, but with no upregulation of target chaperone proteins. Activity of the eIF2α/ATF4 signaling arm increased at the final stage of HSV-1 replication, which may indicate completion of virion assembly and egress, thus releasing suppression of the UPR. We also found that the promoter of viral ICP0 was responsive to ER stress, an apparent mimicry of cellular UPR genes. These results suggest that HSV-1 may use ICP0 as a sensor to modulate the cellular stress response.

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Acknowledgement

We would like to thank Randal Kaufman for the IRE1−/− cells, Karen Mossman for the HSV-1 KOS and the 7134 strains, and Ron Prywesfor the pGL3-5 × UPRE-luciferase plasmid. This work was supported by funds from the Canadian Institutes for Health Research and Natural Sciences and Engineering Research Council of Canada.

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  1. Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada, N1G 2W1

    Heather F. Burnett, Timothy E. Audas, Genqing Liang & Rui Ray Lu

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  1. Heather F. Burnett
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  2. Timothy E. Audas
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  3. Genqing Liang
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  4. Rui Ray Lu
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Correspondence to Rui Ray Lu.

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Heather F. Burnett and Timothy E. Audas contributed equally to this work.

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Burnett, H.F., Audas, T.E., Liang, G. et al. Herpes simplex virus-1 disarms the unfolded protein response in the early stages of infection. Cell Stress and Chaperones 17, 473–483 (2012). https://doi.org/10.1007/s12192-012-0324-8

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