DOI: 10.1128/jvi.79.3.1379-1388.2005. Herpes Simplex Virus 1 Infection Activates the Endoplasmic Reticulum Resident Kinase PERK and Mediates eIF-2α Dephosphorylation by the γ <sub>1</sub> 34.5 Protein

Herpes Simplex Virus 1 Infection Activates the Endoplasmic Reticulum Resident Kinase PERK and Mediates eIF-2α Dephosphorylation by the γ 1 34.5 Protein

10.1128/jvi.79.3.1379-1388.2005

Crossref journal-article

American Society for Microbiology

Journal of Virology (235)

Abstract

ABSTRACT The γ 1 34.5 protein of herpes simplex virus (HSV) plays a crucial role in virus infection. Although the double-stranded RNA-dependent protein kinase (PKR) is activated during HSV infection, the γ 1 34.5 protein inhibits the activity of PKR by mediating dephosphorylation of the translation initiation factor eIF-2α. Here we show that HSV infection also induces phosphorylation of an endoplasmic reticulum (ER) resident kinase PERK, a hallmark of ER stress response. The virus-induced phosphorylation of PERK is blocked by cycloheximide but not by phosphonoacetic acid, suggesting that the accumulation of viral proteins in the ER is essential. Notably, the maximal phosphorylation of PERK is delayed in PKR +/+ cells compared to that seen in PKR −/− cells. Further analysis indicates that hyperphosphorylation of eIF-2α caused by HSV is greater in PKR +/+ cells than in PKR −/− cells. However, expression of the γ 1 34.5 protein suppresses the ER stress response caused by virus, dithiothreitol, and thapsigargin as measured by global protein synthesis. Interestingly, the expression of GADD34 stimulated by HSV infection parallels the status of eIF-2α phosphorylation. Together, these observations suggest that regulation of eIF-2α phosphorylation by the γ 1 34.5 protein is an efficient way to antagonize the inhibitory activity of PKR as well as PERK during productive infection.

Bibliography

Cheng, G., Feng, Z., & He, B. (2005). Herpes Simplex Virus 1 Infection Activates the Endoplasmic Reticulum Resident Kinase PERK and Mediates eIF-2Î± Dephosphorylation by the Î³ 1 34.5 Protein. Journal of Virology, 79(3), 1379â1388.

Authors 3

Guofeng Cheng (first)
Zongdi Feng (additional)
Bin He (additional)

References 39 Referenced 141

Dates

Type	When
Created	20 years, 7 months ago (Jan. 13, 2005, 3:08 p.m.)
Deposited	3 years, 6 months ago (March 5, 2022, 4:52 a.m.)
Indexed	1 month ago (Aug. 3, 2025, 6:49 p.m.)
Issued	20 years, 7 months ago (Feb. 1, 2005)
Published	20 years, 7 months ago (Feb. 1, 2005)
Published Print	20 years, 7 months ago (Feb. 1, 2005)

Funders 0

None

BibTeX

@article{Cheng_2005, title={Herpes Simplex Virus 1 Infection Activates the Endoplasmic Reticulum Resident Kinase PERK and Mediates eIF-2α Dephosphorylation by the γ 1 34.5 Protein}, volume={79}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.79.3.1379-1388.2005}, DOI={10.1128/jvi.79.3.1379-1388.2005}, number={3}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Cheng, Guofeng and Feng, Zongdi and He, Bin}, year={2005}, month=feb, pages={1379–1388} }

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