Abstract
The protein encoded by HSRG1 (HSV-1 stimulation-related gene 1) is a virally induced protein expressed in HSV-1-infected cells. We have already reported that HSRG1 is capable of interacting with transcriptional regulator proteins. To further analyze the effects of HSRG1 on the regulation of viral gene transcription, we expressed the HSRG1 protein in transfected cells and found that it postpones the proliferation of HSV-1. CAT (chloramphenicol acetyltransferase) assays also revealed that HSRG1 reduces transcription from HSV-1 promoters. Yeast two-hybrid and immunoprecipitation assays indicated that HSRG1 interacts with Cyclin T2, the regulatory subunit of P-TEFb, which is required for transcription elongation by RNA Pol II (RNAP II), and that amino acid residues 1–420 in Cyclin T2 are important for binding with HSRG1. Fluorescence assays suggested that the cellular localizations of those two proteins are influenced by their interaction. Further analyses with CAT assays revealed that HSRG1 inhibits the transcriptional activation by Cyclin T2 of viral promoters. Our results suggested that the inhibitory effects of HSRG1 on viral replication and proliferation are probably induced by its binding to Cyclin T2. Therefore, it is likely that HSRG1 inhibits viral gene transcriptional elongation by interacting with Cyclin T2.
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References
Weir J P. Regulation of herpes simplex virus gene expression. Gene, 2001, 271: 117–130 11418233, 10.1016/S0378-1119(01)00512-1, 1:CAS:528:DC%2BD3MXksVWjt7w%3D
Shimomura Y. Herpes simplex virus latency, reactivation, and a new antiviral therapy for herpetic keratitis. Nippon Ganka Gakkai Zasshi, 2008, 112: 247–264 18411713, 1:CAS:528:DC%2BD1cXmtVaqsrg%3D
Minagawa H. Latency and reactivation of human alpha herpesviruses. Nippon Rinsho, 2006, 64, Suppl 3: 192–197
Herbst-Kralovetz M, Pyles R. Toll-like receptors, innate immunity and HSV pathogenesis. Herpes, 2006, 13: 37–41 16895653, 1:STN:280:DC%2BD28vnt12gtg%3D%3D
Li J F, Liu L D, Ma S H, et al. HTRP—an immediate-early gene product induced by HSV1 infection in human embryo fibroblasts, is involved in cellular co-repressors. J Biochem, 2004, 136: 169–176 15496587, 10.1093/jb/mvh108, 1:CAS:528:DC%2BD2cXpslKrsLw%3D
Li Q H. Cytokines and Immediate Early Genes Reactions. Kunming: Yunnan University Press, 2001. 34–57
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. Acta Virol, 2003, 47: 27–32 12828340, 1:CAS:528:DC%2BD3sXks1yjs7o%3D
Cottage A, Edwards Y J, Elgar G, et al. A new protein family: From nucleic acid to protein structure and function prediction. Comp Funct Genomics, 2001, 2: 226–235 18628914, 10.1002/cfg.93, 1:CAS:528:DC%2BD3MXmvVyls7k%3D
Poteryaev D, Spang A. A role of SAND-family proteins in endocytosis. Biochem Soc Trans, 2005, 33: 606–608 16042554, 10.1042/BST0330606, 1:CAS:528:DC%2BD2MXmvFSntbs%3D
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 17109635, 10.1111/j.1365-2184.2006.00408.x, 1:CAS:528:DC%2BD2sXks1Olsg%3D%3D
Marshall N F, Price D H. Purification of P-TEFb, a transcription factor required for the transition into productive elongation. J Biol Chem, 1995, 270: 12335–12338 7759473, 10.1074/jbc.270.44.26303, 1:CAS:528:DyaK2MXlvFOitr8%3D
Marshall N F, Peng J, Xie Z, et al. Control of RNA polymerase II elongation potential by a novel carboxyl-terminal domain kinase. J Biol Chem, 1996, 271: 27176–27183 8900211, 10.1074/jbc.271.43.27176, 1:CAS:528:DyaK28XmsFSisb8%3D
Yu X, Li W Z, Liu L D, 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 10.1007/s11427-008-0127-4, 1:CAS:528:DC%2BD1MXjs1Gjtw%3D%3D
Peng J, Zhu Y, Milton J T, et al. Identification of multiple cyclin subunits of human P-TEFb. Genes Dev, 1998, 12: 755–762 9499409, 10.1101/gad.12.5.755, 1:CAS:528:DyaK1cXitVemur4%3D
Kurosu T, Zhang F, Peterlin B M. Transcriptional activity and substrate recognition of cyclin T2 from P-TEFb. Gene, 2005, 343: 173–179 10.1016/j.gene.2004.08.027
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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. 54, 359–365 (2011). https://doi.org/10.1007/s11427-011-4160-3
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DOI: https://doi.org/10.1007/s11427-011-4160-3