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Journal of Virology, November 2002, p. 11054-11064, Vol. 76, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.21.11054-11064.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Inhibition of PACT-Mediated Activation of PKR by the Herpes Simplex Virus Type 1 Us11 Protein

Gregory A. Peters,1,2 David Khoo,3 Ian Mohr,3 and Ganes C. Sen1,2*

Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195,1 Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106,2 Department of Microbiology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 100163

Received 31 May 2002/ Accepted 15 July 2002

PACT, a protein activator of PKR, can cause inhibition of cellular protein synthesis and apoptosis. Here, we report that the Us11 protein of herpes simplex virus type 1 can block PKR activation by PACT both in vitro and in vivo. Although Us11 can bind to both PKR and PACT, mutational analyses revealed that the binding of Us11 to PKR, and not to PACT, was essential for its inhibitory action. Similar analyses also revealed that the inhibitory effect was mediated by an interaction between the C-terminal half of Us11 and the N-terminal domain of PKR. The binding of Us11 to PKR did not block the binding of PKR to PACT but prevented its activation. Us11 is the first example of a viral protein that can inhibit the action of PACT on PKR.

* Corresponding author. Mailing address: Department of Molecular Biology/NC20, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195. Phone: (216) 444-0636. Fax: (216) 444-0513. E-mail: seng{at}ccf.org.

Journal of Virology, November 2002, p. 11054-11064, Vol. 76, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.21.11054-11064.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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