DOI: 10.1128/jvi.76.5.2029-2035.2002. The Herpes Simplex Virus Type 1 U <sub>S</sub> 11 Protein Interacts with Protein Kinase R in Infected Cells and Requires a 30-Amino-Acid Sequence Adjacent to a Kinase Substrate Domain

The Herpes Simplex Virus Type 1 U S 11 Protein Interacts with Protein Kinase R in Infected Cells and Requires a 30-Amino-Acid Sequence Adjacent to a Kinase Substrate Domain

10.1128/jvi.76.5.2029-2035.2002

Crossref journal-article

American Society for Microbiology

Journal of Virology (235)

Abstract

ABSTRACT The herpes simplex virus type 1 γ 1 34.5 gene product precludes the host-mediated protein shutoff response induced by activated protein kinase R (PKR). Earlier studies demonstrated that recombinant viruses lacking the γ 1 34.5 gene (Δγ 1 34.5) developed secondary mutations that allowed earlier U S 11 expression and enabled continued protein synthesis. Further, in vitro studies demonstrated that a recombinant expressed U S 11 protein binds PKR, blocks the phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF-2α) by activated PKR, and, if provided prior to PKR activation, precluded PKR autophosphorylation. The present study furthers the hypothesis that early U S 11 production precludes PKR-mediated host protein shutoff by demonstrating that (i) U S 11 and PKR interact in the context of viral infection, (ii) this interaction is RNA dependent and requires a 30-amino-acid domain (amino acids 91 to 121) in the carboxyl domain of the U S 11 protein, (iii) the proteins biochemically colocalize in the S100 ribosomal fraction, and (iv) there is a PKR substrate domain immediately adjacent to the binding domain. The results suggest that the U S 11 interaction with PKR at the ribosome is RNA dependent and that the U S 11 protein contains a substrate domain with homology to eIF-2α in close proximity to an essential binding domain.

Bibliography

Cassady, K. A., & Gross, M. (2002). The Herpes Simplex Virus Type 1 U S 11 Protein Interacts with Protein Kinase R in Infected Cells and Requires a 30-Amino-Acid Sequence Adjacent to a Kinase Substrate Domain. Journal of Virology, 76(5), 2029â2035.

Authors 2

Kevin A. Cassady (first)
Martin Gross (additional)

References 31 Referenced 92

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Dates

Type	When
Created	23 years, 1 month ago (July 27, 2002, 5:56 a.m.)
Deposited	3 years, 6 months ago (March 5, 2022, 11:08 a.m.)
Indexed	1 month, 3 weeks ago (July 16, 2025, 9:36 a.m.)
Issued	23 years, 6 months ago (March 1, 2002)
Published	23 years, 6 months ago (March 1, 2002)
Published Print	23 years, 6 months ago (March 1, 2002)

Funders 0

None

BibTeX

@article{Cassady_2002, title={The Herpes Simplex Virus Type 1 U S 11 Protein Interacts with Protein Kinase R in Infected Cells and Requires a 30-Amino-Acid Sequence Adjacent to a Kinase Substrate Domain}, volume={76}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.76.5.2029-2035.2002}, DOI={10.1128/jvi.76.5.2029-2035.2002}, number={5}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Cassady, Kevin A. and Gross, Martin}, year={2002}, month=mar, pages={2029–2035} }

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