Previous Article | Next Article 
Journal of Virology, April 2005, p. 4120-4131, Vol. 79, No. 7
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.7.4120-4131.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Control of VP16 Translation by the Herpes Simplex Virus Type 1 Immediate-Early Protein ICP27
Kimberly S. Ellison,
Robert A. Maranchuk,
Kelly L. Mottet, and
James R. Smiley*
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada
Received 30 September 2004/
Accepted 18 November 2004
Herpes simplex virus (HSV) ICP27 is an essential and multifunctional regulator of gene expression that modulates the synthesis and maturation of viral and cellular mRNAs. Processes that are affected by ICP27 include transcription, pre-mRNA splicing, polyadenylation, and nuclear RNA export. We have examined how ICP27 influences the expression of the essential HSV tegument protein and transactivator of immediate-early gene expression VP16. We monitored the effects of ICP27 on the levels, nuclear export, and polyribosomal association of VP16 mRNA and on the amount and stability of VP16 protein. Deletion of ICP27 reduced the levels of VP16 mRNA without altering its nuclear export or the stability of the encoded protein. However, the translational yield of the VP16 mRNA produced in the absence of ICP27 was reduced 9- to 80-fold relative to that for wild-type infection, suggesting a defect in translation. In the absence of ICP27, the majority of cytoplasmic VP16 mRNA was not associated with actively translating polyribosomes but instead cosedimented with 40S ribosomal subunits, indicating that the translational defect is likely at the level of initiation. These effects were mRNA specific, as polyribosomal analysis of two cellular transcripts (glyceraldehyde-3-phosphate dehydrogenase and ß-actin) and two early HSV transcripts (thymidine kinase and ICP8) indicated that ICP27 is not required for efficient translation of these mRNAs. Thus, we have uncovered a novel mRNA-specific translational regulatory function of ICP27.
* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, 632 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2. Phone: (780) 492-4070. Fax: (780) 492-9828. E-mail:
jim.smiley{at}ualberta.ca.
Journal of Virology, April 2005, p. 4120-4131, Vol. 79, No. 7
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.7.4120-4131.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Rojas, S., Corbin-Lickfett, K. A., Escudero-Paunetto, L., Sandri-Goldin, R. M.
(2010). ICP27 Phosphorylation Site Mutants Are Defective in Herpes Simplex Virus 1 Replication and Gene Expression. J. Virol.
84: 2200-2211
[Abstract]
[Full Text]
-
Aoyagi, M., Gaspar, M., Shenk, T. E.
(2010). Human cytomegalovirus UL69 protein facilitates translation by associating with the mRNA cap-binding complex and excluding 4EBP1. Proc. Natl. Acad. Sci. USA
107: 2640-2645
[Abstract]
[Full Text]
-
Dobrikova, E., Shveygert, M., Walters, R., Gromeier, M.
(2010). Herpes Simplex Virus Proteins ICP27 and UL47 Associate with Polyadenylate-Binding Protein and Control Its Subcellular Distribution. J. Virol.
84: 270-279
[Abstract]
[Full Text]
-
Ricci, E. P., Mure, F., Gruffat, H., Decimo, D., Medina-Palazon, C., Ohlmann, T., Manet, E.
(2009). Translation of intronless RNAs is strongly stimulated by the Epstein-Barr virus mRNA export factor EB2. Nucleic Acids Res
37: 4932-4943
[Abstract]
[Full Text]
-
Gillis, P. A., Okagaki, L. H., Rice, S. A.
(2009). Herpes Simplex Virus Type 1 ICP27 Induces p38 Mitogen-Activated Protein Kinase Signaling and Apoptosis in HeLa Cells. J. Virol.
83: 1767-1777
[Abstract]
[Full Text]
-
Duffy, C., Mbong, E. F., Baines, J. D.
(2009). VP22 of Herpes Simplex Virus 1 Promotes Protein Synthesis at Late Times in Infection and Accumulation of a Subset of Viral mRNAs at Early Times in Infection. J. Virol.
83: 1009-1017
[Abstract]
[Full Text]
-
Sedlackova, L., Perkins, K. D., Lengyel, J., Strain, A. K., van Santen, V. L., Rice, S. A.
(2008). Herpes Simplex Virus Type 1 ICP27 Regulates Expression of a Variant, Secreted Form of Glycoprotein C by an Intron Retention Mechanism. J. Virol.
82: 7443-7455
[Abstract]
[Full Text]
-
Fontaine-Rodriguez, E. C., Knipe, D. M.
(2008). Herpes Simplex Virus ICP27 Increases Translation of a Subset of Viral Late mRNAs. J. Virol.
82: 3538-3545
[Abstract]
[Full Text]
-
Bryant, K. F., Coen, D. M.
(2008). Inhibition of Translation by a Short Element in the 5' Leader of the Herpes Simplex Virus 1 DNA Polymerase Transcript. J. Virol.
82: 77-85
[Abstract]
[Full Text]
-
Corcoran, J. A., Hsu, W.-L., Smiley, J. R.
(2006). Herpes Simplex Virus ICP27 Is Required for Virus-Induced Stabilization of the ARE-Containing IEX-1 mRNA Encoded by the Human IER3 Gene. J. Virol.
80: 9720-9729
[Abstract]
[Full Text]
-
Sanchez, V., Spector, D. H.
(2006). Cyclin-Dependent Kinase Activity Is Required for Efficient Expression and Posttranslational Modification of Human Cytomegalovirus Proteins and for Production of Extracellular Particles. J. Virol.
80: 5886-5896
[Abstract]
[Full Text]
-
Dai-Ju, J. Q., Li, L., Johnson, L. A., Sandri-Goldin, R. M.
(2006). ICP27 Interacts with the C-Terminal Domain of RNA Polymerase II and Facilitates Its Recruitment to Herpes Simplex Virus 1 Transcription Sites, Where It Undergoes Proteasomal Degradation during Infection. J. Virol.
80: 3567-3581
[Abstract]
[Full Text]
-
Larralde, O., Smith, R. W. P., Wilkie, G. S., Malik, P., Gray, N. K., Clements, J. B.
(2006). Direct Stimulation of Translation by the Multifunctional Herpesvirus ICP27 Protein. J. Virol.
80: 1588-1591
[Abstract]
[Full Text]
-
Schwartz, J. A., Brittle, E. E., Reynolds, A. E., Enquist, L. W., Silverstein, S. J.
(2006). UL54-Null Pseudorabies Virus Is Attenuated in Mice but Productively Infects Cells in Culture. J. Virol.
80: 769-784
[Abstract]
[Full Text]