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Journal of Virology, September 2003, p. 10154-10161, Vol. 77, No. 18
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.18.10154-10161.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Dephosphorylation of eIF-2{alpha} Mediated by the {gamma}134.5 Protein of Herpes Simplex Virus Type 1 Is Required for Viral Response to Interferon but Is Not Sufficient for Efficient Viral Replication

Guofeng Cheng, Kui Yang, and Bin He*

Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612

Received 14 March 2003/ Accepted 23 June 2003

The {gamma}134.5 protein of herpes simplex virus type 1 (HSV-1) functions to block the shutoff of protein synthesis involving double-stranded RNA-dependent protein kinase (PKR). In this process, the {gamma}134.5 protein recruits cellular protein phosphatase 1 (PP1) to form a high-molecular-weight complex that dephosphorylates eIF-2{alpha}. Here we show that the {gamma}134.5 protein is capable of mediating eIF-2{alpha} dephosphorylation without any other viral proteins. While deletion of amino acids 1 to 52 from the {gamma}134.5 protein has no effect on eIF-2{alpha} dephosphorylation, further truncations up to amino acid 146 dramatically reduce the activity of the {gamma}134.5 protein. An additional truncation up to amino acid 188 is deleterious, indicating that the carboxyl-terminal domain alone is not functional. Like wild-type HSV-1, the {gamma}134.5 mutant with a truncation of amino acids 1 to 52 is resistant to interferon, and resistance to interferon is coupled to eIF-2{alpha} dephosphorylation. Intriguingly, this mutant exhibits a similar growth defect seen for the {gamma}134.5 null mutant in infected cells. Restoration of the wild-type {gamma}134.5 gene in the recombinant completely reverses the phenotype. These results indicate that eIF-2{alpha} dephosphorylation mediated by the {gamma}134.5 protein is required for HSV response to interferon but is not sufficient for viral replication. Additional functions or activities of the {gamma}134.5 protein contribute to efficient viral infection.

* Corresponding author. Mailing address: Department of Microbiology and Immunology (M/C 790), College of Medicine, University of Illinois at Chicago, 835 S. Wolcott Ave., Chicago, IL 60612. Phone: (312) 996-2391. Fax: (312) 996-6415. E-mail: tshuo{at}uic.edu.

Journal of Virology, September 2003, p. 10154-10161, Vol. 77, No. 18
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.18.10154-10161.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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