Abstract
Herpes Simplex Virus 1 (HSV1) is capable of inducing two forms of infection in individuals, and the establishment of which type of infection occurs is linked to the transcriptional activation of viral α genes. One of the HSV1 α genes, ICP22, is known to have multiple functions during virus replication, but its distinct roles are still unclear. This study showed that ICP22 functions as a general repressor for certain viral and cellular promoters, and this transcriptional repression by ICP22 is independent of the specific upstream promoter element, as shown using the CAT enzyme assay system. Further work also found that VP16 interfered with ICP22 mediated transcriptional repression of the viral α4 gene, through interactions with specific elements upstream of the α4 gene promoter. These findings support the possibility that ICP22 and VP16 control transcription of HSV1α genes in a common pathway for the establishment of either viral lytic or latent infections.
Similar content being viewed by others
References
Honess R W, Roizman B. Regulation of herpesvirus macromolecular synthesis. I. Cascade regulation of the synthesis of three groups of viral proteins. J Virol, 1974, 14(1): 8–19 4365321, 1:CAS:528:DyaE2cXltlalsbg%3D
Carter K I, Roizman B. Alternatively spliced mRNAs predicted to yield frame-shift proteins and stable intron 1 RNAs of the herpes simplex virus 1 regulatory gene alpha 0 accumulate in the cytoplasm of infected cells. Proc Natl Acad Sci USA, 1996, 93: 12535–12540 8901617, 10.1073/pnas.93.22.12535, 1:CAS:528:DyaK28Xms1GhtLY%3D
Advani S J, Brandimarti R, Weichselbaum R R, et al. The disappearance of cyclins A and B and the increase in activity of the G2/M-phase cellular kinase cdc2 in herpes simplex virus 1infected cells require expression of the a22/US1.5 and UL13 viral genes. J Virol, 2000, 74: 8–15 10590085, 10.1128/JVI.74.1.8-15.2000, 1:CAS:528:DC%2BD3cXkvVam
Durand L O, Advani S J, Poon A P W, et al. The carboxyl-terminal domain of RNA polymerase II is phosphorylated by a complex containing cdk9 and infected-cell protein 22 of Herpes Simplex Virus 1. J Virol, 2005, 79(11): 6757–6762 15890914, 10.1128/JVI.79.11.6757-6762.2005, 1:CAS:528:DC%2BD2MXksFKhu78%3D
Jahedi S, Markovitz N S, Filatov F, et al. Colocalization of the herpes simplex virus 1 UL4 protein with infected cell protein 22 in small, dense nuclear structures formed prior to onset of DNA synthesis. J Virol, 1999, 73(6): 5132–5138 10233976, 1:CAS:528:DyaK1MXjtFeqsr4%3D
Fraser K A, Rice S A. Herpes simplex virus immediate-early protein ICP22 triggers loss of serine 2-phosphorylated RNA polymerase II. J Virol, 2007, 81(10): 5091–5101 17344289, 10.1128/JVI.00184-07, 1:CAS:528:DC%2BD2sXls1GrsL0%3D
Rice S A, Long M C, Lam V, et al. Herpes simplex virus immediate-early protein ICP22 is required for viral modification of host RNA polymerase II and establishment of the normal viral transcription program. J Virol, 1995, 69(9): 5550–5559 7637000, 1:CAS:528:DyaK2MXns1Kiur0%3D
Debrus S, Sadzot-Delvaux C, Nikkels A F, et al. Varicella-zoster virus gene 63 encodes an immediate-early protein that is abundantly expressed during latency. J Virol, 1995, 69(5): 3240–3245 7707559, 1:CAS:528:DyaK2MXltVaiu7s%3D
Koppel R, Vogt B, Schwyzer M. Immediate-early protein BICP22 of bovine herpesvirus 1trans-represses viral promoters of different kinetic classes and is itself regulated by BICP0 attranscriptional and posttranscriptional levels. Arch. Virol, 1997, 142(12): 2447–2464 9672606, 10.1007/s007050050254, 1:CAS:528:DyaK1cXhtFCrsrw%3D
Prod’hon C, Machuca I, Berthomme H, et al. Characterization of regulatory functions of the HSV-1 immediate-early protein ICP22. Virology, 1996, 226(2): 393–402 8955059, 10.1006/viro.1996.0667
Cun W, Zhang Y, Liu L D, et al. Analysis of herpes simplex virus type I immediate early gene upstream regulative region. Prog Biochem Biophys, 2006, 33(1): 77–82 1:CAS:528:DC%2BD2sXitlCntL0%3D
Gilinger G, Alwine J C. Transcriptional activation by simian virus 40 large T antigen: requirements for simple promoter structures containing either TATA or initiator elements with variable upstream factor binding sites. J Virol, 1993, 67(11): 6682–6688 8411370, 1:CAS:528:DyaK2cXitF2m
Babb R, Huang C C, Aufiero D J, et al. DNA recognition by the herpes simplex virus transactivator VP16: a novel DNA-binding structure. Mol Cell Biol, 2001, 21(14): 4700–4712 11416146, 10.1128/MCB.21.14.4700-4712.2001, 1:CAS:528:DC%2BD3MXks1Gju7g%3D
Wysocka J, Herr W. The herpes somplex virus VP16-induced complex: the makings of a regulatory switch. Trends Biochem Sci, 2003, 28(6): 294–304 12826401, 10.1016/S0968-0004(03)00088-4, 1:CAS:528:DC%2BD3sXkvVCnu7Y%3D
Sears A E, Halliburton I W, Meignier B, et al. Herpes simplex virus 1 mutant deleted in the alpha 22 gene: growth and gene expression in permissive and restrictive cells and establishment of latency in mice. J Virol, 1985, 55: 338–346 2991560, 1:CAS:528:DyaL2MXlsFGjsrs%3D
Poffenberger K L, Raichlen P E, Herman R C. In vitro characterization of a herpes simplex virus type 1 ICP22 deletion mutant. Virus Genes, 1993, 7: 171–186 8396283, 10.1007/BF01702397, 1:CAS:528:DyaK2cXht12gsL4%3D
Spencer C A, Dahmus M E, Rice S A. Repression of host RNA polymerase II transcription by herpes simplex virus type 1. J Virol, 1997, 71(3): 2031–2040 9032335, 1:CAS:528:DyaK2sXht1Wls7k%3D
Mahajan S S, Little M M, Vazquez R, et al. Interaction of HCF-1 with a Cellular Nuclear Export Factor. J Biol Chem, 2002, 277: 44292–44299 12235138, 10.1074/jbc.M205440200, 1:CAS:528:DC%2BD38Xos1akt7Y%3D
Cohen J I, Krogmann T, Bontems S, et al. Regions of the varicella-zoster virus open reading frame 63 latency-associated protein important for replication in vitro are also critical for efficient establishment of latency. J Virol, 2005, 79(8): 5069–5077 15795292, 10.1128/JVI.79.8.5069-5077.2005, 1:CAS:528:DC%2BD2MXjt1Ght7k%3D
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(6): 1473–1478 14745036, 10.1073/pnas.0307300101, 1:CAS:528:DC%2BD2cXhsFaqsLs%3D
Yang W C, Devi-Rao G V, Ghazal P, et al. General and specific alterations in programming of global viral gene expression during infection by VP16 activation-deficient mutants of herpes simplex virus type 1. J Virol, 2002, 76(24): 12758–12774 12438601, 10.1128/JVI.76.24.12758-12774.2002, 1:CAS:528:DC%2BD38XptVygu7o%3D
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by the National Natural Science Foundation (Grant No. 30570081, 30670094) and Doctoral Fund of Ministry of Education of China (Grant No. 20060023053)
Rights and permissions
About this article
Cite this article
Cun, W., Guo, L., Zhang, Y. et al. Transcriptional regulation of the Herpes Simplex Virus 1α-gene by the viral immediate-early protein ICP22 in association with VP16. SCI CHINA SER C 52, 344–351 (2009). https://doi.org/10.1007/s11427-009-0051-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-009-0051-2