Abstract
Studies of herpes simplex virus type 1 (HSV-1) infection have shown that many known and unknown cellular molecules involved in viral proliferation are up-regulated following HSV-1 infection. In this study, using two-dimensional polyacrylamide gel electrophoresis, we found that the expression of the HSV-1 infection response repressive protein (HIRRP, GI 16552881) was up-regulated in human L02 cells infected with HSV-1. HIRRP, an unknown protein, was initially localized in the cytoplasm and then translocated into the nucleus of HSV-1-infected cells. Further analysis showed that HIRRP represses HSV-1 proliferation by inhibiting transcription of the viral genome by interacting with the cellular transcription factor, ATF5, via its N-terminal domain. ATF5 represses the transcription of many host genes but can also act as an activator of genes containing a specific motif. We found that ATF5 promotes the proliferation of HSV-1 via a potential mechanism by which ATF5 enhances the transcription of viral genes during the course of an HSV-1 infection; HIRRP then induces feedback repression of this transcription by interacting with ATF5.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Reference
Negorev D G, Vladimirova O V, Maul G G. Differential functions of interferon-upregulated Sp100 isoforms: Herpes simplex virus type 1 promoter-based immediate-early gene suppression and PML protection from ICP0-mediated degradation. J Virol, 2009, 83: 5168–5180
Servant M J, Grandvaux N H J. Multiple signaling pathways leading to the activation of interferon regulatory factor 3. Biochem Pharmacol, 2002, 64: 985–992
Kim J C, Lee S Y, Kim S Y, et al. HSV-1 ICP27 suppresses NF-kappaB activity by stabilizing IkappaBalpha. FEBS Lett, 2008, 582: 2371–2376
Lin R, Noyce R S, Collins S E, et al. The herpes simplex virus ICP0 RING finger domain inhibits IRF3- and IRF7-mediated activation of interferon-stimulated genes. J Virol, 2004, 78: 1675–1684
Fossum E, Friedel C C, Rajagopala SV, et al. Evolutionarily conserved herpesviral protein interaction networks. PLoS Pathog, 2009, 5: e1000570
Uetz P, Dong Y A, Zeretzke C, et al. Herpesviral protein networks and their interaction with the human proteome. Science, 2006, 311: 239–242
McGavern D B, Kang S S. Illuminating viral infections in the nervous system. Nat Rev Immunol, 2011, 11: 318–329
Cliffe A R, Garber D A, Knipe D M. Transcription of the herpes simplex virus latency-associated transcript promotes the formation of facultative heterochromatin on lytic promoters. J Virol, 2009, 83: 8182–8190
Divito S, Cherpes T L, Hendricks R L. A triple entente: Virus, neurons, and CD8+ T cells maintain HSV-1 latency. Immunol Res, 2006, 36: 119–126
Cun W, Guo L, Zhang Y, et al. Transcriptional regulation of the Herpes simplex virus 1alpha-gene by the viral immediate-early protein ICP22 in association with VP16. Sci China Ser C-Life Sci, 2009, 52: 344–351
Yu X, Li W, Liu L, et al. Functional analysis of transcriptional regulation of herpes simplex virus type 1 tegument protein VP22. Sci China Ser C-Life Sci, 2008, 51: 966–972
Guo H, Cun W, Liu L, et al. Immediate-early gene product ICP22 inhibits the trans-transcription activating function of P53-mdm-2. Sci China Ser C-Life Sci, 2007, 50: 473–478
Wu W, Yu X, Li W, et al. HSV-1 stimulation-related protein HSRG1 inhibits viral gene transcriptional elongation by interacting with Cyclin T2. Sci China Life Sci, 2011, 54: 359–365
Yu X, Liu L, Wu L, et al. Herpes simplex virus type 1 tegument protein VP22 is capable of modulating the transcription of viral TK and gC genes via interaction with viral ICP0. Biochimie, 2010, 92: 1024–1030
Herrera F J, Triezenberg S J. VP16-dependent association of chromatin-modifying coactivators and underrepresentation of histones at immediate-early gene promoters during herpes simplex virus infection. J Virol, 2004, 78: 9689–9696
Wysocka J, Herr W. The herpes simplex virus VP16-induced complex: The makings of a regulatory switch. Trends Biochem Sci, 2003, 28: 294–304
Luciano R L, Wilson A C. An activation domain in the C-terminal subunit of HCF-1 is important for transactivation by VP16 and LZIP. Proc Natl Acad Sci USA, 2002, 99: 13403–13408
Nogueira M L, Wang V E, Tantin D, et al. Herpes simplex virus infections are arrested in Oct-1-deficient cells. Proc Natl Acad Sci USA, 2004, 101: 1473–1478
Cai W, Schaffer P A. Herpes simplex virus type 1 ICP0 regulates expression of immediate-early, early, and late genes in productively infected cells. J Virol, 1992, 66: 2904–2915
Millhouse S, Wigdahl B. Molecular circuitry regulating herpes simplex virus type 1 latency in neurons. J Neurovirol, 2000, 6: 6–24
Hong M, Che Y C, Tang G Z. Herpes simplex virus 1 infection alters the mRNA translation processing in L-02 cells. Virol Sin, 2008, 23: 43–50
Christensen T. Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses. Rev Med Virol, 2005, 15: 179–211
Umbach J L, Nagel M A, Cohrs R J, et al. Analysis of human alphaherpesvirus microRNA expression in latently infected human trigeminal ganglia. J Virol, 2009, 83: 10677–10683
Roberts A P, Abaitua F, O’Hare P, et al. Differing roles of inner tegument proteins pUL36 and pUL37 during entry of herpes simplex virus type 1. J Virol, 2009, 83: 105–116
Lagos D, Pollara G, Henderson S, et al. miR-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator. Nat Cell Biol, 2010, 12: 513–519
Akhtar J, Shukla D. Viral entry mechanisms: Cellular and viral mediators of herpes simplex virus entry. FEBS J, 2009, 276: 7228–7236
Guo H X, Cun W, Liu L D, et al. Protein encoded by HSV-1 stimulation-related gene 1 (HSRG1) interacts with and inhibits SV40 large T antigen. Cell Prolif, 2006, 39: 507–518
Dong S, Dong C, Liu L, et al. Identification of a novel human sand family protein in human fibroblasts induced by herpes simplex virus 1 binding. 1 binding. Acta Virol, 2003, 47: 27–32
Li Q, Zhao H, Jiang L, et al. An SR-protein induced by HSVI binding to cells functioning as a splicing inhibitor of viral pre-mRNA. J Mol Biol, 2002, 316: 887–894
Kawaguchi Y, Bruni R, Roizman B, et al. Interaction of herpes simplex virus 1 alpha regulatory protein ICP0 with elongation factor 1delta: ICP0 affects translational machinery. J Virol, 1997, 71: 1019–1024
Raczniak G A, Bulkow L R, Bruce M G, et al. Long-term immunogenicity of hepatitis A virus vaccine in Alaska 17 years after initial childhood series. J Infect Dis, 2013, 207: 493–496
Schmittgen T D, Livak K J. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc, 2008, 3: 1101–1108
Li G, Li W, Angelastro J M, et al. Identification of a novel DNA binding site and a transcriptional target for activating transcription factor 5 in C6 glioma and MCF-7 breast cancer cells. Mol Cancer Res, 2009, 7: 933
Persengiev S P, Devireddy L R, Green M R. Inhibition of apoptosis by ATFx: A novel role for a member of the ATF/CREBfamily of mammalian bZIP transcription factors. Genes Dev, 2002, 16: 1806–1814
Davido D J, Leib D A. Analysis of the basal and inducible activities of the ICPO promoter of herpes simplex virus type 1. J Gen Virol, 1998, 79: 2093–2098
Wang H, Lin G, Zhang Z. ATF5 promotes cell survival through transcriptional activation of Hsp27 in H9c2 cells. Cell Biol Int, 2007, 31: 1309–1315
Author information
Authors and Affiliations
Corresponding author
Additional information
This article is published with open access at Springerlink.com
Electronic supplementary material
Rights and permissions
Open Access This article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Wu, L., Zhang, X., Che, Y. et al. A cellular response protein induced during HSV-1 infection inhibits viral replication by interacting with ATF5. Sci. China Life Sci. 56, 1124–1133 (2013). https://doi.org/10.1007/s11427-013-4569-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-013-4569-y