This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cassady, K. A.
Right arrow Articles by Gross, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cassady, K. A.
Right arrow Articles by Gross, M.

Next Article 

Journal of Virology, March 2002, p. 2029-2035, Vol. 76, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/jvi.76.5.2029-2035.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Herpes Simplex Virus Type 1 US11 Protein Interacts with Protein Kinase R in Infected Cells and Requires a 30-Amino-Acid Sequence Adjacent to a Kinase Substrate Domain

*** Kevin A. Cassady1* and Martin Gross2

Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, Alabama 35294 ,1 Department of Pathology, The University of Chicago, Chicago, Illinois 606372

Received 25 July 2001/ Accepted 26 November 2001

The herpes simplex virus type 1 {gamma}134.5 gene product precludes the host-mediated protein shutoff response induced by activated protein kinase R (PKR). Earlier studies demonstrated that recombinant viruses lacking the {gamma}134.5 gene ({Delta}{gamma}134.5) developed secondary mutations that allowed earlier US11 expression and enabled continued protein synthesis. Further, in vitro studies demonstrated that a recombinant expressed US11 protein binds PKR, blocks the phosphorylation of the {alpha} subunit of eukaryotic initiation factor 2 (eIF-2{alpha}) by activated PKR, and, if provided prior to PKR activation, precluded PKR autophosphorylation. The present study furthers the hypothesis that early US11 production precludes PKR-mediated host protein shutoff by demonstrating that (i) US11 and PKR interact in the context of viral infection, (ii) this interaction is RNA dependent and requires a 30-amino-acid domain (amino acids 91 to 121) in the carboxyl domain of the US11 protein, (iii) the proteins biochemically colocalize in the S100 ribosomal fraction, and (iv) there is a PKR substrate domain immediately adjacent to the binding domain. The results suggest that the US11 interaction with PKR at the ribosome is RNA dependent and that the US11 protein contains a substrate domain with homology to eIF-2{alpha} in close proximity to an essential binding domain.

* Corresponding author. Mailing address: UAB Department of Pediatrics, 845 19th St. South, BBRB-309, Birmingham, AL 35294. Phone: (205) 934-6750. Fax: (205) 975-1992. E-mail: kcassady{at}peds.uab.edu.

Journal of Virology, March 2002, p. 2029-2035, Vol. 76, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/jvi.76.5.2029-2035.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wylie, K. M., Schrimpf, J. E., Morrison, L. A. (2009). Increased eIF2{alpha} Phosphorylation Attenuates Replication of Herpes Simplex Virus 2 vhs Mutants in Mouse Embryonic Fibroblasts and Correlates with Reduced Accumulation of the PKR Antagonist ICP34.5. J. Virol. 83: 9151-9162 [Abstract] [Full Text]  
  • Wakimoto, H., Kesari, S., Farrell, C. J., Curry, W. T. Jr., Zaupa, C., Aghi, M., Kuroda, T., Stemmer-Rachamimov, A., Shah, K., Liu, T.-C., Jeyaretna, D. S., Debasitis, J., Pruszak, J., Martuza, R. L., Rabkin, S. D. (2009). Human Glioblastoma-Derived Cancer Stem Cells: Establishment of Invasive Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors. Cancer Res. 69: 3472-3481 [Abstract] [Full Text]  
  • Budt, M., Niederstadt, L., Valchanova, R. S., Jonjic, S., Brune, W. (2009). Specific Inhibition of the PKR-Mediated Antiviral Response by the Murine Cytomegalovirus Proteins m142 and m143. J. Virol. 83: 1260-1270 [Abstract] [Full Text]  
  • Liang, L., Roizman, B. (2008). Expression of Gamma Interferon-Dependent Genes Is Blocked Independently by Virion Host Shutoff RNase and by US3 Protein Kinase. J. Virol. 82: 4688-4696 [Abstract] [Full Text]  
  • Ambagala, A. P. N., Cohen, J. I. (2007). Varicella-Zoster Virus IE63, a Major Viral Latency Protein, Is Required To Inhibit the Alpha Interferon-Induced Antiviral Response. J. Virol. 81: 7844-7851 [Abstract] [Full Text]  
  • Jaworska, J., Gravel, A., Fink, K., Grandvaux, N., Flamand, L. (2007). Inhibition of Transcription of the Beta Interferon Gene by the Human Herpesvirus 6 Immediate-Early 1 Protein. J. Virol. 81: 5737-5748 [Abstract] [Full Text]  
  • Garcia, M. A., Gil, J., Ventoso, I., Guerra, S., Domingo, E., Rivas, C., Esteban, M. (2006). Impact of Protein Kinase PKR in Cell Biology: from Antiviral to Antiproliferative Action. Microbiol. Mol. Biol. Rev. 70: 1032-1060 [Abstract] [Full Text]  
  • Desloges, N., Rahaus, M., Wolff, M. H. (2005). Role of the protein kinase PKR in the inhibition of varicella-zoster virus replication by beta interferon and gamma interferon. J. Gen. Virol. 86: 1-6 [Abstract] [Full Text]  
  • Mulvey, M., Camarena, V., Mohr, I. (2004). Full Resistance of Herpes Simplex Virus Type 1-Infected Primary Human Cells to Alpha Interferon Requires both the Us11 and {gamma}134.5 Gene Products. J. Virol. 78: 10193-10196 [Abstract] [Full Text]  
  • Giraud, S., Diaz-Latoud, C., Hacot, S., Textoris, J., Bourette, R. P., Diaz, J.-J. (2004). US11 of Herpes Simplex Virus Type 1 Interacts with HIPK2 and Antagonizes HIPK2-Induced Cell Growth Arrest. J. Virol. 78: 2984-2993 [Abstract] [Full Text]  
  • Adams, O., Besken, K., Oberdorfer, C., MacKenzie, C. R., Takikawa, O., Daubener, W. (2004). Role of Indoleamine-2,3-Dioxygenase in Alpha/Beta and Gamma Interferon-Mediated Antiviral Effects against Herpes Simplex Virus Infections. J. Virol. 78: 2632-2636 [Abstract] [Full Text]  
  • Mulvey, M., Poppers, J., Sternberg, D., Mohr, I. (2003). Regulation of eIF2{alpha} Phosphorylation by Different Functions That Act during Discrete Phases in the Herpes Simplex Virus Type 1 Life Cycle. J. Virol. 77: 10917-10928 [Abstract] [Full Text]  
  • Benboudjema, L., Mulvey, M., Gao, Y., Pimplikar, S. W., Mohr, I. (2003). Association of the Herpes Simplex Virus Type 1 Us11 Gene Product with the Cellular Kinesin Light-Chain-Related Protein PAT1 Results in the Redistribution of Both Polypeptides. J. Virol. 77: 9192-9203 [Abstract] [Full Text]  
  • 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 eIF2{alpha} Phosphorylation. J. Virol. 77: 4626-4634 [Abstract] [Full Text]  
  • Poppers, J., Mulvey, M., Perez, C., Khoo, D., Mohr, I. (2002). Identification of a Lytic-Cycle Epstein-Barr Virus Gene Product That Can Regulate PKR Activation. J. Virol. 77: 228-236 [Abstract] [Full Text]  
  • Khoo, D., Perez, C., Mohr, I. (2002). Characterization of RNA Determinants Recognized by the Arginine- and Proline-Rich Region of Us11, a Herpes Simplex Virus Type 1-Encoded Double-Stranded RNA Binding Protein That Prevents PKR Activation. J. Virol. 76: 11971-11981 [Abstract] [Full Text]  
  • Peters, G. A., Khoo, D., Mohr, I., Sen, G. C. (2002). Inhibition of PACT-Mediated Activation of PKR by the Herpes Simplex Virus Type 1 Us11 Protein. J. Virol. 76: 11054-11064 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»