Skip to main content
SpringerLink
Log in

The Human CMV IE1 Protein: An Offender of PML Nuclear Bodies

  • Chapter
  • First Online:
Cell Biology of Herpes Viruses

Part of the book series: Advances in Anatomy, Embryology and Cell Biology ((ADVSANAT,volume 223))

Abstract

PML nuclear bodies (PML-NBs) are SUMOylation-dependent, highly complex protein assemblies that accumulate in the interchromosomal territories of the cell nucleus. Research of the last two decades revealed that many viruses have evolved effector proteins that modify PML-NBs. This correlates with antagonization of individual PML-NB components which act as host cell restriction factors. The multifunctional immediate-early protein IE1 of human cytomegalovirus directly interacts with the PML protein resulting in a disruption of the dot-like structure of PML-NBs. This review summarizes recent advances on the functional consequences of PML-NB modification by IE1. In particular, we describe that PML exerts a novel co-regulatory role during the interferon response which is abrogated by IE1. Via binding to PML, IE1 is able to compromise both intrinsic antiviral defense mechanisms and classical innate immune responses. These interactions of IE1 with innate host defenses are crucial for the onset of lytic replication and, consequently, may represent promising targets for antiviral strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Adler M, Tavalai N, Muller R, Stamminger T (2011) Human cytomegalovirus immediate-early gene expression is restricted by the nuclear domain 10 component Sp100. J Gen Virol 92:1532–1538

    Article  CAS  PubMed  Google Scholar 

  • Ahn JH, Hayward GS (1997) The major immediate-early proteins IE1 and IE2 of human cytomegalovirus colocalize with and disrupt PML-associated nuclear bodies at very early times in infected permissive cells. J Virol 71:4599–4613

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ahn JH, Brignole EJ III, Hayward GS (1998) Disruption of PML subnuclear domains by the acidic IE1 protein of human cytomegalovirus is mediated through interaction with PML and may modulate a RING finger-dependent cryptic transactivator function of PML. Mol Cell Biol 18:4899–4913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bernardi R, Pandolfi PP (2007) Structure, dynamics and functions of promyelocytic leukaemia nuclear bodies. Nat Rev Mol Cell Biol 8:1006–1016

    Article  CAS  PubMed  Google Scholar 

  • Boshart M, Weber F, Jahn G, Dorsch-Hasler K, Fleckenstein B, Schaffner W (1985) A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus. Cell 41:521–530

    Article  CAS  PubMed  Google Scholar 

  • Bottomley MJ, Collard MW, Huggenvik JI, Liu Z, Gibson TJ, Sattler M (2001) The SAND domain structure defines a novel DNA-binding fold in transcriptional regulation. Nat Struct Biol 8:626–633

    Article  CAS  PubMed  Google Scholar 

  • Boutell C, Cuchet-Lourenco D, Vanni E, Orr A, Glass M, McFarlane S, Everett RD (2011) A viral ubiquitin ligase has substrate preferential SUMO targeted ubiquitin ligase activity that counteracts intrinsic antiviral defence. PLoS Pathog 7:e1002245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carbone R, Botrugno OA, Ronzoni S, Insinga A, Di Croce L, Pelicci PG, Minucci S (2006) Recruitment of the histone methyltransferase SUV39H1 and its role in the oncogenic properties of the leukemia-associated PML-retinoic acid receptor fusion protein. Mol Cell Biol 26:1288–1296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang CC, Lin DY, Fang HI, Chen RH, Shih HM (2005) Daxx mediates the small ubiquitin-like modifier-dependent transcriptional repression of Smad4. J Biol Chem 280:10164–10173

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Wright J, Meng X, Leppard KN (2015) Promyelocytic leukemia protein isoform II promotes transcription factor recruitment to activate interferon beta and interferon-responsive gene expression. Mol Cell Biol 35:1660–1672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dent AL, Yewdell J, Puvion-Dutilleul F, Koken MH, de The H, Staudt LM (1996) LYSP100-associated nuclear domains (LANDs): description of a new class of subnuclear structures and their relationship to PML nuclear bodies. Blood 88:1423–1426

    CAS  PubMed  Google Scholar 

  • Di Croce L, Raker VA, Corsaro M, Fazi F, Fanelli M, Faretta M, Fuks F, Lo CF, Kouzarides T, Nervi C, Minucci S, Pelicci PG (2002) Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science 295:1079–1082

    Article  PubMed  Google Scholar 

  • Dyck JA, Maul GG, Miller WH Jr, Chen JD, Kakizuka A, Evans RM (1994) A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein. Cell 76:333–343

    Article  CAS  PubMed  Google Scholar 

  • El Asmi F, Maroui MA, Dutrieux J, Blondel D, Nisole S, Chelbi-Alix MK (2014) Implication of PMLIV in both intrinsic and innate immunity. PLoS Pathog 10:e1003975

    Article  PubMed  PubMed Central  Google Scholar 

  • Fang Q, Chen P, Wang M, Fang J, Yang N, Li G, Xu RM (2016) Human cytomegalovirus IE1 protein alters the higher-order chromatin structure by targeting the acidic patch of the nucleosome. Elife 5:e11911

    PubMed  PubMed Central  Google Scholar 

  • Goldstone DC, Walker PA, Calder LJ, Coombs PJ, Kirkpatrick J, Ball NJ, Hilditch L, Yap MW, Rosenthal PB, Stoye JP, Taylor IA (2014) Structural studies of postentry restriction factors reveal antiparallel dimers that enable avid binding to the HIV-1 capsid lattice. Proc Natl Acad Sci USA 111:9609–9614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Greaves RF, Mocarski ES (1998) Defective growth correlates with reduced accumulation of a viral DNA replication protein after low-multiplicity infection by a human cytomegalovirus ie1 mutant. J Virol 72:366–379

    CAS  PubMed  PubMed Central  Google Scholar 

  • Groves IJ, Reeves MB, Sinclair JH (2009) Lytic infection of permissive cells with human cytomegalovirus is regulated by an intrinsic ‘pre-immediate-early’ repression of viral gene expression mediated by histone post-translational modification. J Gen Virol 90:2364–2374

    Article  CAS  PubMed  Google Scholar 

  • Guldner HH, Szostecki C, Schroder P, Matschl U, Jensen K, Luders C, Will H, Sternsdorf T (1999) Splice variants of the nuclear dot-associated Sp100 protein contain homologies to HMG-1 and a human nuclear phosphoprotein-box motif. J Cell Sci 112(Pt 5):733–747

    CAS  PubMed  Google Scholar 

  • Hattersley N, Shen L, Jaffray EG, Hay RT (2011) The SUMO protease SENP6 is a direct regulator of PML nuclear bodies. Mol Biol Cell 22:78–90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hollenbach AD, Sublett JE, McPherson CJ, Grosveld G (1999) The Pax3-FKHR oncoprotein is unresponsive to the Pax3-associated repressor hDaxx. EMBO J 18:3702–3711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hollenbach AD, McPherson CJ, Mientjes EJ, Iyengar R, Grosveld G (2002) Daxx and histone deacetylase II associate with chromatin through an interaction with core histones and the chromatin-associated protein Dek. J Cell Sci 115:3319–3330

    CAS  PubMed  Google Scholar 

  • Huh YH, Kim YE, Kim ET, Park JJ, Song MJ, Zhu H, Hayward GS, Ahn JH (2008) Binding STAT2 by the acidic domain of human cytomegalovirus IE1 promotes viral growth and is negatively regulated by SUMO. J Virol 82:10444–10454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ishov AM, Stenberg RM, Maul GG (1997) Human cytomegalovirus immediate early interaction with host nuclear structures: definition of an immediate transcript environment. J Cell Biol 138:5–16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ishov AM, Sotnikov AG, Negorev D, Vladimirova OV, Neff N, Kamitani T, Yeh ETH, Strauss JF, Maul GG (1999) PML is critical for ND10 formation and recruits the PML-interacting protein Daxx to this nuclear structure when modified by SUMO-1. J Cell Biol 147:221–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ishov AM, Vladimirova OV, Maul GG (2004) Heterochromatin and ND10 are cell-cycle regulated and phosphorylation-dependent alternate nuclear sites of the transcription repressor Daxx and SWI/SNF protein ATRX. J Cell Sci 117:3807–3820

    Article  CAS  PubMed  Google Scholar 

  • Ivanschitz L, Takahashi Y, Jollivet F, Ayrault O, Le Bras M, de Thé H (2015) PML IV/ARF interaction enhances p53 SUMO-1 conjugation, activation, and senescence. Proc Natl Acad Sci USA 112:14278–14283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jang MS, Ryu SW, Kim E (2002) Modification of Daxx by small ubiquitin-related modifier-1. Biochem Biophys Res Commun 295:495–500

    Article  CAS  PubMed  Google Scholar 

  • Kakizuka A, Miller WH Jr, Umesono K, Warrell RP Jr, Frankel SR, Murty VV, Dmitrovsky E, Evans RM (1991) Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell 66:663–674

    Article  CAS  PubMed  Google Scholar 

  • Kim YE, Ahn JH (2015) Positive role of promyelocytic leukemia protein in type I interferon response and its regulation by human cytomegalovirus. PLoS Pathog 11:e1004785

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim EJ, Park JS, Um SJ (2003) Identification of Daxx interacting with p73, one of the p53 family, and its regulation of p53 activity by competitive interaction with PML. Nucleic Acids Res 31:5356–5367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kiriakidou M, Driscoll DA, Lopez-Guisa JM, Strauss JF III (1997) Cloning and expression of primate Daxx cDNAs and mapping of the human gene to chromosome 6p21.3 in the MHC region. DNA Cell Biol 16:1289–1298

    Article  CAS  PubMed  Google Scholar 

  • Korioth F, Maul GG, Plachter B, Stamminger T, Frey J (1996) The nuclear domain 10 (ND10) is disrupted by the human cytomegalovirus gene product IE1. Exp Cell Res 229:155–158

    Article  CAS  PubMed  Google Scholar 

  • Krauss S, Kaps J, Czech N, Paulus C, Nevels M (2009) Physical requirements and functional consequences of complex formation between the cytomegalovirus IE1 protein and human STAT2. J Virol 83:12854–12870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lallemand-Breitenbach V, Jeanne M, Benhenda S, Nasr R, Lei M, Peres L, Zhou J, Zhu J, Raught B, de Thé H (2008) Arsenic degrades PML or PML-RARalpha through a SUMO-triggered RNF4/ubiquitin-mediated pathway. Nat Cell Biol 10:547–555

    Article  CAS  PubMed  Google Scholar 

  • Lee HR, Kim DJ, Lee JM, Choi CY, Ahn BY, Hayward GS, Ahn JH (2004) Ability of the human cytomegalovirus IE1 protein to modulate sumoylation of PML correlates with its functional activities in transcriptional regulation and infectivity in cultured fibroblast cells. J Virol 78:6527–6542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li H, Leo C, Zhu J, Wu X, O’Neil J, Park EJ, Chen JD (2000a) Sequestration and inhibition of Daxx-mediated transcriptional repression by PML. Mol Cell Biol 20:1784–1796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li R, Pei H, Watson DK, Papas TS (2000b) EAP1/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes. Oncogene 19:745–753

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Wu H, Wu W, Zhuo W, Liu W, Zhang Y, Cheng M, Chen YG, Gao N, Yu H, Wang L, Li W, Yang M (2014) Structural insights into the TRIM family of ubiquitin E3 ligases. Cell Res 24:762–765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang YC, Lee CC, Yao YL, Lai CC, Schmitz ML, Yang WM (2016) SUMO5, a novel poly-SUMO isoform, regulates PML nuclear bodies. Sci Rep 6:26509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin DY, Huang YS, Jeng JC, Kuo HY, Chang CC, Chao TT, Ho CC, Chen YC, Lin TP, Fang HI, Hung CC, Suen CS, Hwang MJ, Chang KS, Maul GG, Shih HM (2006) Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors. Mol Cell 24:341–354

    Article  CAS  PubMed  Google Scholar 

  • Liu B, Stinski MF (1992) Human cytomegalovirus contains a tegument protein that enhances transcription from promoters with upstream ATF and AP-1 cis-acting elements. J Virol 66:4434–4444

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lo YH, Huang YW, Wu YH, Tsai CS, Lin YC, Mo ST, Kuo WC, Chuang YT, Jiang ST, Shih HM, Lai MZ (2013) Selective inhibition of the NLRP3 inflammasome by targeting to promyelocytic leukemia protein in mouse and human. Blood 121:3185–3194

    Article  CAS  PubMed  Google Scholar 

  • Lukashchuk V, McFarlane S, Everett RD, Preston CM (2008) Human cytomegalovirus protein pp71 displaces the chromatin-associated factor ATRX from nuclear domain 10 at early stages of infection. J Virol 82:12543–12554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lunardi A, Gaboli M, Giorgio M, Rivi R, Bygrave A, Antoniou M, Drabek D, Dzierzak E, Fagioli M, Salmena L, Botto M, Cordon-Cardo C, Luzzatto L, Pelicci PG, Grosveld F, Pandolfi PP (2011) A role for PML in innate immunity. Genes Cancer 2:10–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maarifi G, Chelbi-Alix MK, Nisole S (2014) PML control of cytokine signaling. Cytokine Growth Factor Rev 25:551–561

    Article  CAS  PubMed  Google Scholar 

  • Malone CL, Vesole DH, Stinski MF (1990) Transactivation of a human cytomegalovirus early promoter by gene products from the immediate-early gene IE2 and augmentation by IE1: mutational analysis of the viral proteins. J Virol 64:1498–1506

    CAS  PubMed  PubMed Central  Google Scholar 

  • Marchini A, Liu H, Zhu H (2001) Human cytomegalovirus with IE-2 (UL122) deleted fails to express early lytic genes. J Virol 75:1870–1878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matunis MJ, Zhang XD, Ellis NA (2006) SUMO: the glue that binds. Dev Cell 11:596–597

    Article  CAS  PubMed  Google Scholar 

  • Maul GG, Ishov AM, Everett RD (1996) Nuclear domain 10 as preexisting potential replication start sites of herpes simplex virus type-1. Virology 217:67–75

    Article  CAS  PubMed  Google Scholar 

  • Michaelson JS (2000) The Daxx enigma. Apoptosis 5:217–220

    Article  CAS  PubMed  Google Scholar 

  • Michaelson JS, Leder P (2003) RNAi reveals anti-apoptotic and transcriptionally repressive activities of DAXX. J Cell Sci 116:345–352

    Article  CAS  PubMed  Google Scholar 

  • Mocarski ES, Kemble GW, Lyle JM, Greaves RF (1996) A deletion mutant in the human cytomegalovirus gene encoding IE1(491aa) is replication defective due to a failure in autoregulation. Proc Natl Acad Sci USA 93:11321–11326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muller S, Dejean A (1999) Viral immediate-early proteins abrogate the modification by SUMO-1 of PML and Sp100 proteins, correlating with nuclear body disruption. J Virol 73:5137–5143

    CAS  PubMed  PubMed Central  Google Scholar 

  • Muller S, Matunis MJ, Dejean A (1998) Conjugation with the ubiquitin-related modifier SUMO-1 regulates the partitioning of PML within the nucleus. EMBO J 17:61–70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muromoto R, Sugiyama K, Takachi A, Imoto S, Sato N, Yamamoto T, Oritani K, Shimoda K, Matsuda T (2004) Physical and functional interactions between Daxx and DNA methyltransferase 1-associated protein, DMAP1. J Immunol 172:2985–2993

    Article  CAS  PubMed  Google Scholar 

  • Negorev D, Maul GG (2001) Cellular proteins localized at and interacting within ND10/PML nuclear bodies/PODs suggest functions of a nuclear depot. Oncogene 20:7234–7242

    Article  CAS  PubMed  Google Scholar 

  • Ohsaki Y, Kawai T, Yoshikawa Y, Cheng J, Jokitalo E, Fujimoto T (2016) PML isoform II plays a critical role in nuclear lipid droplet formation. J Cell Biol 212:29–38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park J, Lee JH, La M, Jang MJ, Chae GW, Kim SB, Tak H, Jung Y, Byun B, Ahn JK, Joe CO (2007) Inhibition of NF-kappaB acetylation and its transcriptional activity by Daxx. J Mol Biol 368:388–397

    Article  CAS  PubMed  Google Scholar 

  • Paulus C, Krauss S, Nevels M (2006) A human cytomegalovirus antagonist of type I IFN-dependent signal transducer and activator of transcription signaling. Proc Natl Acad Sci USA 103:3840–3845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peng G, Lei KJ, Jin W, Greenwell-Wild T, Wahl SM (2006) Induction of APOBEC3 family proteins, a defensive maneuver underlying interferon-induced anti-HIV-1 activity. J Exp Med 203:41–46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pizzorno MC, O’Hare P, Sha L, LaFemina RL, Hayward GS (1988) Trans-activation and autoregulation of gene expression by the immediate-early region 2 gene products of human cytomegalovirus. J Virol 62:1167–1179

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pluta AF, Earnshaw WC, Goldberg IG (1998) Interphase-specific association of intrinsic centromere protein CENP-C with HDaxx, a death domain-binding protein implicated in Fas-mediated cell death. J Cell Sci 111(Pt 14):2029–2041

    CAS  PubMed  Google Scholar 

  • Rabellino A, Carter B, Konstantinidou G, Wu SY, Rimessi A, Byers LA, Heymach JV, Girard L, Chiang CM, Teruya-Feldstein J, Scaglioni PP (2012) The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML and its oncogenic counterpart PML-RARA. Cancer Res 72:2275–2284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rajsbaum R, Garcia-Sastre A, Versteeg GA (2014) TRIMmunity: the roles of the TRIM E3-ubiquitin ligase family in innate antiviral immunity. J Mol Biol 426:1265–1284

    Article  CAS  PubMed  Google Scholar 

  • Regad T, Chelbi-Alix MK (2001) Role and fate of PML nuclear bodies in response to interferon and viral infections. Oncogene 20:7274–7286

    Article  CAS  PubMed  Google Scholar 

  • Reinhardt J, Smith GB, Himmelheber CT, Zizkhan-Clifford J, Mocarski ES (2005) The carboxyl-terminal region of human cytomegalovirus IE1491aa contains an acidic domain that plays a regulatory role and a chromatin-tethering domain that is dispensable during viral replication. J Virol 79:225–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saffert RT, Kalejta RF (2006) Inactivating a cellular intrinsic immune defense mediated by Daxx is the mechanism through which the human cytomegalovirus pp71 protein stimulates viral immediate-early gene expression. J Virol 80:3863–3871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salomoni P, Khelifi AF (2006) Daxx: death or survival protein? Trends Cell Biol 16:97–104

    Article  CAS  PubMed  Google Scholar 

  • Sanchez JG, Okreglicka K, Chandrasekaran V, Welker JM, Sundquist WI, Pornillos O (2014) The tripartite motif coiled-coil is an elongated antiparallel hairpin dimer. Proc Natl Acad Sci USA 111:2494–2499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scherer M, Stamminger T (2016) Emerging role of PML nuclear bodies in innate immune signaling. J Virol 90:5850–5854

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scherer M, Reuter N, Wagenknecht N, Otto V, Sticht H, Stamminger T (2013) Small ubiquitin-related modifier (SUMO) pathway-mediated enhancement of human cytomegalovirus replication correlates with a recruitment of SUMO-1/3 proteins to viral replication compartments. J Gen Virol 94:1373–1384

    Article  CAS  PubMed  Google Scholar 

  • Scherer M, Klingl S, Sevvana M, Otto V, Schilling EM, Stump JD, Muller R, Reuter N, Sticht H, Muller YA, Stamminger T (2014) Crystal structure of cytomegalovirus IE1 protein reveals targeting of TRIM family member PML via coiled-coil interactions. PLoS Pathog 10:e1004512

    Article  PubMed  PubMed Central  Google Scholar 

  • Scherer M, Otto V, Stump JD, Klingl S, Muller R, Reuter N, Muller YA, Sticht H, Stamminger T (2016) Characterization of recombinant human cytomegaloviruses encoding IE1 mutants L174P and 1-382 reveals that viral targeting of PML bodies perturbs both intrinsic and innate immune responses. J Virol 90:1190–1205

    Article  CAS  PubMed Central  Google Scholar 

  • Schierling K, Stamminger T, Mertens T, Winkler M (2004) Human cytomegalovirus tegument proteins ppUL82 (pp71) and ppUL35 interact and cooperatively activate the major immediate-early enhancer. J Virol 78:9512–9523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seeler JS, Marchio A, Sitterlin D, Transy C, Dejean A (1998) Interaction of SP100 with HP1 proteins: a link between the promyelocytic leukemia-associated nuclear bodies and the chromatin compartment. Proc Natl Acad Sci USA 95:7316–7321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seeler JS, Marchio A, Losson R, Desterro JM, Hay RT, Chambon P, Dejean A (2001) Common properties of nuclear body protein SP100 and TIF1alpha chromatin factor: role of SUMO modification. Mol Cell Biol 21:3314–3324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shen TH, Lin HK, Scaglioni PP, Yung TM, Pandolfi PP (2006) The mechanisms of PML-nuclear body formation. Mol Cell 24:331–339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sinclair J (2010) Chromatin structure regulates human cytomegalovirus gene expression during latency, reactivation and lytic infection. Biochim Biophys Acta 1799:286–295

    Article  CAS  PubMed  Google Scholar 

  • Stamminger T, Gstaiger M, Weinzierl K, Lorz K, Winkler M, Schaffner W (2002) Open reading frame UL26 of human cytomegalovirus encodes a novel tegument protein that contains a strong transcriptional activation domain. J Virol 76:4836–4847

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stenberg RM (1996) The human cytomegalovirus major immediate-early gene. Intervirology 39:343–349

    Article  CAS  PubMed  Google Scholar 

  • Sternsdorf T, Jensen K, Will H (1997) Evidence for covalent modification of the nuclear dot-associated proteins PML and Sp100 by PIC1/SUMO-1. J Cell Biol 139:1621–1634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sternsdorf T, Jensen K, Reich B, Will H (1999) The nuclear dot protein sp100, characterization of domains necessary for dimerization, subcellular localization, and modification by small ubiquitin-like modifiers. J Biol Chem 274:12555–12566

    Article  CAS  PubMed  Google Scholar 

  • Szostecki C, Guldner HH, Netter HJ, Will H (1990) Isolation and characterization of cDNA encoding a human nuclear antigen predominantly recognized by autoantibodies from patients with primary biliary cirrhosis. J Immunol 145:4338–4347

    CAS  PubMed  Google Scholar 

  • Tavalai N, Stamminger T (2009) Interplay between herpesvirus infection and host defense by PML nuclear bodies. Viruses 1:1240–1264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tavalai N, Stamminger T (2011) Intrinsic cellular defense mechanisms targeting human cytomegalovirus. Virus Res 157:128–133

    Article  CAS  PubMed  Google Scholar 

  • Tavalai N, Papior P, Rechter S, Leis M, Stamminger T (2006) Evidence for a role of the cellular ND10 protein PML in mediating intrinsic immunity against human cytomegalovirus infections. J Virol 80:8006–8018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tavalai N, Papior P, Rechter S, Stamminger T (2008) Nuclear domain 10 components promyelocytic leukemia protein and hDaxx independently contribute to an intrinsic antiviral defense against human cytomegalovirus infection. J Virol 82:126–137

    Article  CAS  PubMed  Google Scholar 

  • Ulbricht T, Alzrigat M, Horch A, Reuter N, von Mikecz A, Steimle V, Schmitt E, Kramer OH, Stamminger T, Hemmerich P (2012) PML promotes MHC class II gene expression by stabilizing the class II transactivator. J Cell Biol 199:49–63

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Van Damme E, Laukens K, Dang TH, Van Ostade X (2010) A manually curated network of the PML nuclear body interactome reveals an important role for PML-NBs in SUMOylation dynamics. Int J Biol Sci 6:51–67

    Article  PubMed  PubMed Central  Google Scholar 

  • Voon HP, Wong LH (2016) New players in heterochromatin silencing: histone variant H3.3 and the ATRX/DAXX chaperone. Nucleic Acids Res 44:1496–1501

    Article  PubMed  PubMed Central  Google Scholar 

  • Wilcox KW, Sheriff S, Isaac A, Taylor JL (2005) SP100B is a repressor of gene expression. J Cell Biochem 95:352–365

    Article  CAS  PubMed  Google Scholar 

  • Wilkinson GW, Kelly C, Sinclair JH, Rickards C (1998) Disruption of PML-associated nuclear bodies mediated by the human cytomegalovirus major immediate early gene product. J Gen Virol 79(Pt 5):1233–1245

    Article  CAS  PubMed  Google Scholar 

  • Woodhall DL, Groves IJ, Reeves MB, Wilkinson G, Sinclair JH (2006) Human Daxx-mediated repression of human cytomegalovirus gene expression correlates with a repressive chromatin structure around the major immediate early promoter. J Biol Chem 281:37652–37660

    Article  CAS  PubMed  Google Scholar 

  • Wu WS, Vallian S, Seto E, Yang WM, Edmondson D, Roth S, Chang KS (2001) The growth suppressor PML represses transcription by functionally and physically interacting with histone deacetylases. Mol Cell Biol 21:2259–2268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu Y, Ahn JH, Cheng M, ApRhys CM, Chiou CJ, Zong J, Matunis MJ, Hayward GS (2001) Proteasome-independent disruption of PML oncogenic domains (PODs), but not covalent modification by SUMO-1, is required for human cytomegalovirus immediate-early protein IE1 to inhibit PML-mediated transcriptional repression. J Virol 75:10683–10695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xue Y, Gibbons R, Yan Z, Yang D, McDowell TL, Sechi S, Qin J, Zhou S, Higgs D, Wang W (2003) The ATRX syndrome protein forms a chromatin-remodeling complex with Daxx and localizes in promyelocytic leukemia nuclear bodies. Proc Natl Acad Sci USA 100:10635–10640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zalckvar E, Paulus C, Tillo D, Asbach-Nitzsche A, Lubling Y, Winterling C, Strieder N, Mucke K, Goodrum F, Segal E, Nevels M (2013) Nucleosome maps of the human cytomegalovirus genome reveal a temporal switch in chromatin organization linked to a major IE protein. Proc Natl Acad Sci USA 110:13126–13131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgment

We would like to thank Dr. Stefan Klingl for help with the manuscript. Work presented in this article was supported by the Deutsche Forschungsgemeinschaft (DFG, SFB796, B3) and the Interdisziplinäre Zentrum für Klinische Forschung Erlangen (IZKF Erlangen, project A61).

Author information

Authors and Affiliations

  1. Institute for Clinical and Molecular Virology, Friedrich-Alexander-Universtität (FAU) Erlangen-Nürnberg, Erlangen, Germany

    Myriam Scherer, Eva-Maria Schilling & Thomas Stamminger

Authors
  1. Myriam Scherer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eva-Maria Schilling
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas Stamminger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Stamminger .

Editor information

Editors and Affiliations

  1. Institut für Virologie, Freie Universität Berlin, Berlin, Germany

    Klaus Osterrieder

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Scherer, M., Schilling, EM., Stamminger, T. (2017). The Human CMV IE1 Protein: An Offender of PML Nuclear Bodies. In: Osterrieder, K. (eds) Cell Biology of Herpes Viruses. Advances in Anatomy, Embryology and Cell Biology, vol 223. Springer, Cham. https://doi.org/10.1007/978-3-319-53168-7_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-53168-7_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-53167-0

  • Online ISBN: 978-3-319-53168-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation