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Journal of Virology, December 2009, p. 12626-12630, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01431-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Dephosphorylation of eIF2{alpha} Mediated by the {gamma}134.5 Protein of Herpes Simplex Virus 1 Facilitates Viral Neuroinvasion {triangledown}

Dustin Verpooten,1 Zongdi Feng,1 Tibor Valyi-Nagy,2 Yijie Ma,1 Huali Jin,1 Zhipeng Yan,1 Cuizhu Zhang,3 Youjia Cao,3* and Bin He1*

Department of Microbiology and Immunology,1 Department of Pathology, College of Medicine, University of Illinois, Chicago, Illinois 60612,2 Tianjin Key Laboratory of Protein Sciences, College of Life Sciences, Nankai University, Tianjin 300071, People's Republic of China3

Received 10 July 2009/ Accepted 10 September 2009

The {gamma}134.5 protein, a virulence factor of herpes simplex viruses, redirects protein phosphatase 1 to dephosphorylate the {alpha} subunit of translation initiation factor 2 (eIF2{alpha}). Additionally, it inhibits the induction of antiviral genes by TANK-binding kinase 1. Nevertheless, its precise role in vivo remains to be established. Here we show that eIF2{alpha} dephosphorylation by {gamma}134.5 is crucial for viral neuroinvasion. V193E and F195L substitutions in {gamma}134.5 abrogate viral replication in the eye and spread to the trigeminal ganglia and brain. Intriguingly, inhibition of antiviral gene induction by {gamma}134.5 is not sufficient to exhibit viral virulence.

* Corresponding author. Mailing address for Bin He: Department of Microbiology and Immunology (M/C 790), College of Medicine, the University of Illinois at Chicago, 835 South Wolcott Avenue, Chicago, IL 60612. Phone: (312) 996-2391. Fax: (312) 996-6415. E-mail: tshuo{at}uic.edu. Mailing address for Youjia Cao: Nankai University, Tianjin Key Laboratory of Protein Sciences, College of Life Sciences, Tianjin 300071, PR China. Phone and fax: 82-22-23500808. E-mail: caoyj{at}nankai.edu.cn

{triangledown} Published ahead of print on 16 September 2009.

Journal of Virology, December 2009, p. 12626-12630, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01431-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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