DOI: 10.1128/jvi.77.8.4626-4634.2003. In Vivo Replication of an ICP34.5 Second-Site Suppressor Mutant following Corneal Infection Correlates with In Vitro Regulation of eIF2α Phosphorylation

In Vivo Replication of an ICP34.5 Second-Site Suppressor Mutant following Corneal Infection Correlates with In Vitro Regulation of eIF2α Phosphorylation

10.1128/jvi.77.8.4626-4634.2003

Crossref journal-article

American Society for Microbiology

Journal of Virology (235)

Abstract

ABSTRACT In animal models of herpes simplex virus type 1 (HSV-1) infection, ICP34.5-null viruses are avirulent and also fail to grow in a variety of cultured cells due to their inability to prevent RNA-dependent protein kinase (PKR)-mediated inhibition of protein synthesis. We show here that the inability of ICP34.5 mutants to grow in vitro is due specifically to the accumulation of phosphorylated eIF2α. Mutations suppressing the in vitro phenotype of ICP34.5-null mutants have been described which map to the unique short region of the HSV-1 genome, resulting in dysregulated expression of the US11 gene. Despite the inability of the suppressor mutation to suppress the avirulent phenotype of the ICP34.5-null parental virus following intracranial inoculation, the suppressor mutation enhanced virus growth in the cornea, trigeminal ganglia, and periocular skin following corneal infection compared to that with the ICP34.5-null virus. The phosphorylation state of eIF2α following in vitro infection with the suppressor virus was examined to determine if in vivo differences could be attributed to differential regulation of eIF2α phosphorylation. The suppressor virus prevented accumulation of phosphorylated eIF2α, while the wild-type virus substantially reduced eIF2α phosphorylation levels. These data suggest that US11 functions as a PKR antagonist in vivo, although its activity may be modulated by tissue-specific differences in translation regulation.

Bibliography

Ward, S. L., Scheuner, D., Poppers, J., Kaufman, R. J., Mohr, I., & Leib, D. A. (2003). In Vivo Replication of an ICP34.5 Second-Site Suppressor Mutant following Corneal Infection Correlates with In Vitro Regulation of eIF2Î± Phosphorylation. Journal of Virology, 77(8), 4626â4634.

Authors 6

Stephen L. Ward (first)
Donalyn Scheuner (additional)
Jeremy Poppers (additional)
Randal J. Kaufman (additional)
Ian Mohr (additional)
David A. Leib (additional)

References 45 Referenced 22

Dates

Type	When
Created	22 years, 5 months ago (March 27, 2003, 12:23 p.m.)
Deposited	3 years, 6 months ago (March 5, 2022, 3:24 a.m.)
Indexed	1 week, 6 days ago (Aug. 23, 2025, 9:08 p.m.)
Issued	22 years, 4 months ago (April 15, 2003)
Published	22 years, 4 months ago (April 15, 2003)
Published Print	22 years, 4 months ago (April 15, 2003)

Funders 0

None

BibTeX

@article{Ward_2003, title={In Vivo Replication of an ICP34.5 Second-Site Suppressor Mutant following Corneal Infection Correlates with In Vitro Regulation of eIF2α Phosphorylation}, volume={77}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.77.8.4626-4634.2003}, DOI={10.1128/jvi.77.8.4626-4634.2003}, number={8}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Ward, Stephen L. and Scheuner, Donalyn and Poppers, Jeremy and Kaufman, Randal J. and Mohr, Ian and Leib, David A.}, year={2003}, month=apr, pages={4626–4634} }

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