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Journal of Virology, July 2008, p. 6098-6108, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.02121-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Cell-Type-Specific Tyrosine Phosphorylation of the Herpes Simplex Virus Tegument Protein VP11/12 Encoded by Gene UL46{triangledown}

George Zahariadis,1,2,3,§ Melany J. Wagner,1,§ Rosalyn C. Doepker,1 Jessica M. Maciejko,1 Carly M. Crider,4 Keith R. Jerome,4 and James R. Smiley1*

Alberta Institute for Viral Immunology, Department of Medical Microbiology and Immunology,1 Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2,2 Provincial Laboratory for Public Health (Microbiology), Edmonton, Alberta, Canada T6G 2J2,3 Department of Laboratory Medicine and Vaccine and Infectious Disease Institute, University of Washington, and Fred Hutchison Cancer Research Center, Seattle, Washington 981954

Received 25 September 2007/ Accepted 9 April 2008

Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells play key roles in limiting herpesvirus infections; consequently, many herpesviruses, including herpes simplex virus (HSV), have evolved diverse strategies to evade and/or disarm these killer lymphocytes. Previous studies have shown that CTL and NK cells are functionally inactivated following contact with HSV-infected fibroblasts. During studies of the mechanisms involved, we discovered that HSV-inactivated NK-92 NK cells and Jurkat T cells contain a strikingly prominent, novel, ca. 90-kDa tyrosine-phosphorylated protein that we identified as the HSV tegument protein VP11/12. Inasmuch as VP11/12 produced in fibroblasts and epithelial cells is not obviously tyrosine phosphorylated, these data suggested that VP11/12 serves as the substrate of a cell-type-specific protein tyrosine kinase. Consistent with this hypothesis, VP11/12 was also tyrosine phosphorylated in B lymphocytes, and this modification was severely reduced in Jurkat T cells lacking the lymphocyte-specific Src family kinase Lck. These findings demonstrate that HSV tegument proteins can be differentially modified depending on the cell type infected. Our data also raise the possibility that VP11/12 may modulate one or more lymphocyte-specific signaling pathways or serve another lymphocyte-specific function. However, HSV type 1 mutants lacking the UL46 gene retained the ability to block signaling through the T-cell receptor in Jurkat cells and remained competent to functionally inactivate the NK-92 NK cell line, indicating that VP11/12 is not essential for lymphocyte inactivation. Further studies are therefore required to determine the biological function of tyrosine-phosphorylated VP11/12.

* Corresponding author. Mailing address: Alberta Institute for Viral Immunology, Department of Medical Microbiology and Immunology, University of Alberta, 632 Heritage Medical Research Center, Edmonton, Alberta T6G 2S2, Canada. Phone: (780) 492-4070. Fax: (780) 492-9828. E-mail: jim.smiley{at}ualberta.ca

{triangledown} Published ahead of print on 16 April 2008.

§ G.Z. and M.J.W. contributed equally to this work.

Journal of Virology, July 2008, p. 6098-6108, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.02121-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wagner, M. J., Smiley, J. R. (2009). Herpes Simplex Virus Requires VP11/12 To Induce Phosphorylation of the Activation Loop Tyrosine (Y394) of the Src Family Kinase Lck in T Lymphocytes. J. Virol. 83: 12452-12461 [Abstract] [Full Text]  


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