Advanced search
Publication Cover
Future Virology Volume 7, 2012 - Issue 9
Submit an article Journal homepage
42
Views
0
CrossRef citations to date
0
Altmetric
Review

Tale of a Tegument Transactivator: The Past, Present and Future of Human CMV pp71

Rhiannon R Penkert1 Institute for Molecular Virology & McArdle Laboratory for Cancer Research, University of Wisconsin–Madison, 1525 Linden Drive, Madison, WI53706, USAView further author information
&
Robert F Kalejta1 Institute for Molecular Virology & McArdle Laboratory for Cancer Research, University of Wisconsin–Madison, 1525 Linden Drive, Madison, WI53706, USACorrespondence[email protected]
View further author information
Pages 855-869 | Published online: 21 Sep 2012

References

  • Boeckh M , GeballeAP. Cytomegalovirus: pathogen, paradigm, and puzzle. J. Clin. Invest.121(5) , 1673–1680 (2011).
  • Reeves M , SinclairJ. Aspects of human cytomegalovirus latency and reactivation. Curr. Top. Microbiol. Immunol.325 , 297–313 (2008).
  • Goodrum F , CavinessK, ZagalloP. Human cytomegalovirus persistence. Cell. Microbiol.14(5) , 644–655 (2012).
  • Mocarski E , ShenkT, PassR. Cytomegaloviruses. In: Fields Virology, Howley P (Ed.). Lippincott, PA, USA, 2701–2772 (2007).
  • Mendelson M , MonardS, SissonsP, SinclairJ. Detection of endogenous human cytomegalovirus in CD34+ bone marrow progenitors. J. Gen. Virol.77(Pt 12) , 3099–3102 (1996).
  • Hahn G , JoresR, MocarskiES. Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells. Proc. Natl Acad. Sci. USA95(7) , 3937–3942 (1998).
  • Sindre H , TjoonnfjordGE, RollagH et al. Human cytomegalovirus suppression of and latency in early hematopoietic progenitor cells. Blood 88(12) , 4526–4533 (1996).
  • Maciejewski JP , BrueningEE, DonahueRE, MocarskiES, YoungNS, St Jeor SC. Infection of hematopoietic progenitor cells by human cytomegalovirus. Blood80(1) , 170–178 (1992).
  • Cheshier SH , MorrisonSJ, LiaoX, WeissmanIL. In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. Proc. Natl Acad. Sci. USA96(6) , 3120–3125 (1999).
  • Murphy E , YuD, GrimwoodJ et al. Coding potential of laboratory and clinical strains of human cytomegalovirus. Proc. Natl Acad. Sci. USA 100(25) , 14976–14981 (2003).
  • Kalejta RF . Tegument proteins of human cytomegalovirus. Microbiol. Mol. Biol. Rev.72(2) , 249–265 (2008).
  • Bresnahan WA , ShenkTE. UL82 virion protein activates expression of immediate early viral genes in human cytomegalovirus-infected cells. Proc. Natl Acad. Sci. USA97(26) , 14506–14511 (2000).
  • Liu B , StinskiMF. Human cytomegalovirus contains a tegument protein that enhances transcription from promoters with upstream ATF and AP-1 cis-acting elements. J. Virol.66(7) , 4434–4444 (1992).
  • Chee MS , BankierAT, BeckS et al. Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169. Curr. Top. Microbiol. Immunol. 154 , 125–169 (1990).
  • Sarov I , AbadyI. The morphogenesis of human cytomegalovirus. Isolation and polypeptide characterization of cytomegalovirions and dense bodies. Virology66(2) , 464–473 (1975).
  • Irmiere A , GibsonW. Isolation and characterization of a noninfectious virion-like particle released from cells infected with human strains of cytomegalovirus. Virology130(1) , 118–133 (1983).
  • Nowak B , SullivanC, SarnowP et al. Characterization of monoclonal antibodies and polyclonal immune sera directed against human cytomegalovirus virion proteins. Virology 132(2) , 325–338 (1984).
  • Roby C , GibsonW. Characterization of phosphoproteins and protein kinase activity of virions, noninfectious enveloped particles, and dense bodies of human cytomegalovirus. J. Virol.59(3) , 714–727 (1986).
  • Hensel GM , MeyerHH, BuchmannI et al. Intracellular localization and expression of the human cytomegalovirus matrix phosphoprotein pp71 (ppUL82): evidence for its translocation into the nucleus. J. Gen. Virol. 77(Pt 12) , 3087–3097 (1996).
  • Nowak B , GmeinerA, SarnowP, LevineAJ, FleckensteinB. Physical mapping of human cytomegalovirus genes: identification of DNA sequences coding for a virion phosphoprotein of 71 kDa and a viral 65-kDa polypeptide. Virology134(1) , 91–102 (1984).
  • Ruger B , KlagesS, WallaB et al. Primary structure and transcription of the genes coding for the two virion phosphoproteins pp65 and pp71 of human cytomegalovirus. J. Virol. 61(2) , 446–453 (1987).
  • Gatherer D , SeirafianS, CunninghamC et al. High-resolution human cytomegalovirus transcriptome. Proc. Natl Acad. Sci. USA 108(49) , 19755–19760 (2011).
  • Bego M , MaciejewskiJ, KhaiboullinaS, PariG, St Jeor S. Characterization of an antisense transcript spanning the UL81–82 locus of human cytomegalovirus. J. Virol.79(17) , 11022–11034 (2005).
  • Murphy E , ShenkT. Human cytomegalovirus genome. Curr. Top. Microbiol. Immunol.325 , 1–19 (2008).
  • Dal Monte P , BessiaC, RipaltiA et al. Stably expressed antisense RNA to cytomegalovirus UL83 inhibits viral replication. J. Virol. 70(4) , 2086–2094 (1996).
  • Bego MG , KeyesLR, MaciejewskiJ, St Jeor SC. Human cytomegalovirus latency-associated protein LUNA is expressed during HCMV infections in vivo. Arch. Virol.156(10) , 1847–1851 (2011).
  • Reeves MB , SinclairJH. Analysis of latent viral gene expression in natural and experimental latency models of human cytomegalovirus and its correlation with histone modifications at a latent promoter. J. Gen. Virol.91(Pt 3) , 599–604 (2010).
  • Umbach JL , KramerMF, JurakI, KarnowskiHW, CoenDM, CullenBR. MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs. Nature454(7205) , 780–783 (2008).
  • Davison AJ , StowND. New genes from old: redeployment of dUTPase by herpesviruses. J. Virol.79(20) , 12880–12892 (2005).
  • Lewis PW , ElsaesserSJ, NohKM, StadlerSC, AllisCD. Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres. Proc. Natl Acad. Sci. USA107(32) , 14075–14080 (2010).
  • Michaelson JS . The Daxx enigma. Apoptosis5(3) , 217–220 (2000).
  • Hofmann H , SindreH, StammingerT. Functional interaction between the pp71 protein of human cytomegalovirus and the PML-interacting protein human Daxx. J. Virol.76(11) , 5769–5783 (2002).
  • Ishov AM , VladimirovaOV, MaulGG. Daxx-mediated accumulation of human cytomegalovirus tegument protein pp71 at ND10 facilitates initiation of viral infection at these nuclear domains. J. Virol.76(15) , 7705–7712 (2002).
  • Kalejta RF , BechtelJT, ShenkT. Human cytomegalovirus pp71 stimulates cell cycle progression by inducing the proteasome-dependent degradation of the retinoblastoma family of tumor suppressors. Mol. Cell. Biol.23(6) , 1885–1895 (2003).
  • Lee SH , KalejtaRF, KerryJ et al. BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection. Proc. Natl Acad. Sci. USA 109(24) , 9575–9580 (2012).
  • Maere S , HeymansK, KuiperM. BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics21(16) , 3448–3449 (2005).
  • Schierling K , StammingerT, MertensT, WinklerM. Human cytomegalovirus tegument proteins ppUL82 (pp71) and ppUL35 interact and cooperatively activate the major immediate–early enhancer. J. Virol.78(17) , 9512–9523 (2004).
  • Phillips SL , BresnahanWA. Identification of binary interactions between human cytomegalovirus virion proteins. J. Virol.85(1) , 440–447 (2010).
  • To A , BaiY, ShenA et al. Yeast two hybrid analyses reveal novel binary interactions between human cytomegalovirus-encoded virion proteins. PLoS One 6(4) , e17796 (2011).
  • Marshall KR , RowleyKV, RinaldiA et al. Activity and intracellular localization of the human cytomegalovirus protein pp71. J. Gen. Virol. 83(Pt 7) , 1601–1612 (2002).
  • Shen W , WestgardE, HuangL et al. Nuclear trafficking of the human cytomegalovirus pp71 (ppUL82) tegument protein. Virology 376(1) , 42–52 (2008).
  • Penkert RR , KalejtaRF. Nuclear localization of tegument-delivered pp71 in human cytomegalovirus-infected cells is facilitated by one or more factors present in terminally differentiated fibroblasts. J. Virol.84(19) , 9853–9863 (2010).
  • Saffert R , PenkertR, KalejtaR. Cellular and viral control over the initial events of human cytomegalovirus experimental latency in CD34+ cells. J. Virol.84(11) , 5594–5604 (2010).
  • Saffert RT , KalejtaRF. Human cytomegalovirus gene expression is silenced by Daxx-mediated intrinsic immune defense in model latent infections established in vitro. J. Virol.81(17) , 9109–9120 (2007).
  • La Boissiere S , HughesT, O‘HareP. HCF-dependent nuclear import of VP16. EMBO J.18(2) , 480–489 (1999).
  • Spaete RR , MocarskiES. Regulation of cytomegalovirus gene expression: alpha and beta promoters are trans activated by viral functions in permissive human fibroblasts. J. Virol.56(1) , 135–143 (1985).
  • Stinski MF , RoehrTJ. Activation of the major immediate early gene of human cytomegalovirus by cis-acting elements in the promoter-regulatory sequence and by virus-specific trans-acting components. J. Virol.55(2) , 431–441 (1985).
  • Baldick CJ Jr, Marchini A, Patterson CE, Shenk T. Human cytomegalovirus tegument protein pp71 (ppUL82) enhances the infectivity of viral DNA and accelerates the infectious cycle. J. Virol.71(6) , 4400–4408 (1997).
  • Borst EM , HahnG, KoszinowskiUH, MesserleM. Cloning of the human cytomegalovirus (HCMV) genome as an infectious bacterial artificial chromosome in Escherichia coli: a new approach for construction of HCMV mutants. J. Virol.73(10) , 8320–8329 (1999).
  • Paredes AM , YuD. Human cytomegalovirus: bacterial artificial chromosome (BAC) cloning and genetic manipulation. Curr. Protoc. Microbiol. Chapter 14, Unit 14E.4 (2012).
  • Biegalke BJ . Human cytomegalovirus US3 gene expression is regulated by a complex network of positive and negative regulators. Virology261(2) , 155–164 (1999).
  • Chau NH , VansonCD, KerryJA. Transcriptional regulation of the human cytomegalovirus US11 early gene. J. Virol.73(2) , 863–870 (1999).
  • Homer EG , RinaldiA, NichollMJ, PrestonCM. Activation of herpesvirus gene expression by the human cytomegalovirus protein pp71. J. Virol.73(10) , 8512–8518 (1999).
  • Preston CM , NichollMJ. Human cytomegalovirus tegument protein pp71 directs long-term gene expression from quiescent herpes simplex virus genomes. J. Virol.79(1) , 525–535 (2005).
  • Schmolke S , KernHF, DrescherP, JahnG, PlachterB. The dominant phosphoprotein pp65 (UL83) of human cytomegalovirus is dispensable for growth in cell culture. J. Virol.69(10) , 5959–5968 (1995).
  • Cantrell SR , BresnahanWA. Interaction between the human cytomegalovirus UL82 gene product (pp71) and hDaxx regulates immediate–early gene expression and viral replication. J. Virol.79(12) , 7792–7802 (2005).
  • Hume AJ , FinkelJS, KamilJP, CoenDM, CulbertsonMR, KalejtaRF. Phosphorylation of retinoblastoma protein by viral protein with cyclin-dependent kinase function. Science320(5877) , 797–799 (2008).
  • Kalejta RF , ShenkT. Proteasome-dependent, ubiquitin-independent degradation of the Rb family of tumor suppressors by the human cytomegalovirus pp71 protein. Proc. Natl Acad. Sci. USA100(6) , 3263–3268 (2003).
  • Saffert RT , KalejtaRF. 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(8) , 3863–3871 (2006).
  • Cantrell SR , BresnahanWA. Human cytomegalovirus (HCMV) UL82 gene product (pp71) relieves hDaxx-mediated repression of HCMV replication. J. Virol.80(12) , 6188–6191 (2006).
  • Preston CM , NichollMJ. Role of the cellular protein hDaxx in human cytomegalovirus immediate–early gene expression. J. Gen. Virol.87(Pt 5) , 1113–1121 (2006).
  • Woodhall DL , GrovesIJ, ReevesMB, WilkinsonG, SinclairJH. 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(49) , 37652–37660 (2006).
  • Kalejta RF . Functions of human cytomegalovirus tegument proteins prior to immediate early gene expression. Curr. Top. Microbiol. Immunol.325 , 101–115 (2008).
  • Hwang J , KalejtaRF. Human cytomegalovirus protein pp71 induces Daxx SUMOylation. J. Virol.83(13) , 6591–6598 (2009).
  • Lukashchuk V , McFarlaneS, EverettRD, PrestonCM. Human cytomegalovirus protein pp71 displaces the chromatin-associated factor ATRX from nuclear domain 10 at early stages of infection. J. Virol.82(24) , 12543–12554 (2008).
  • Slobedman B , CaoJZ, AvdicS et al. Human cytomegalovirus latent infection and associated viral gene expression. Future Microbiol. 5(6) , 883–900 (2010).
  • Keyes LR , BegoMG, SolandM, St Jeor S. Cyclophilin A is required for efficient human cytomegalovirus DNA replication and reactivation. J. Gen. Virol.93(Pt 4) , 722–732 (2012).
  • Liu X , YuanJ, WuAW, McGonagillPW, GalleCS, MeierJL. Phorbol ester-induced human cytomegalovirus major immediate–early (MIE) enhancer activation through PKC-delta, CREB, and NF-kappaB desilences MIE gene expression in quiescently infected human pluripotent NTera2 cells. J. Virol.84(17) , 8495–8508 (2010).
  • Goodrum F , JordanCT, TerhuneSS, HighK, ShenkT. Differential outcomes of human cytomegalovirus infection in primitive hematopoietic cell subpopulations. Blood104(3) , 687–695 (2004).
  • Reeves MB , LehnerPJ, SissonsJG, SinclairJH. An in vitro model for the regulation of human cytomegalovirus latency and reactivation in dendritic cells by chromatin remodelling. J. Gen. Virol.86(Pt 11) , 2949–2954 (2005).
  • Groves IJ , SinclairJH. Knockdown of hDaxx in normally non-permissive undifferentiated cells does not permit human cytomegalovirus immediate–early gene expression. J. Gen. Virol.88(Pt 11) , 2935–2940 (2007).
  • Michaelson JS , BaderD, KuoF, KozakC, LederP. Loss of Daxx, a promiscuously interacting protein, results in extensive apoptosis in early mouse development. Genes Dev.13(15) , 1918–1923 (1999).
  • Penkert RR , KalejtaRF. Tegument protein control of latent herpesvirus establishment and animation. Herpesviridae2(1) , 3 (2011).
  • Thompson RL , PrestonCM, SawtellNM. De novo synthesis of VP16 coordinates the exit from HSV latency in vivo. PLoS Pathog.5(3) , e1000352 (2009).
  • Kalejta RF , ShenkT. Manipulation of the cell cycle by human cytomegalovirus. Front. Biosci.7 , d295–d306 (2002).
  • Kalejta RF , ShenkT. The human cytomegalovirus UL82 gene product (pp71) accelerates progression through the G1 phase of the cell cycle. J. Virol.77(6) , 3451–3459 (2003).
  • Kalejta RF , BrideauAD, BanfieldBW, BeavisAJ. An integral membrane green fluorescent protein marker, Us9-GFP, is quantitatively retained in cells during propidium iodide-based cell cycle analysis by flow cytometry. Exp. Cell Res.248(1) , 322–328 (1999).
  • Kalejta RF , ShenkT, BeavisAJ. Use of a membrane-localized green fluorescent protein allows simultaneous identification of transfected cells and cell cycle analysis by flow cytometry. Cytometry29(4) , 286–291 (1997).
  • Grana X , GarrigaJ, MayolX. Role of the retinoblastoma protein family, pRB, p107 and p130 in the negative control of cell growth. Oncogene17(25) , 3365–3383 (1998).
  • Trimarchi JM , LeesJA. Sibling rivalry in the E2F family. Nat. Rev. Mol. Cell. Biol.3(1) , 11–20 (2002).
  • Adams PD . Regulation of the retinoblastoma tumor suppressor protein by cyclin/cdks. Biochim. Biophys. Acta1471(3) , M123–M133 (2001).
  • Hume AJ , KalejtaRF. Regulation of the retinoblastoma proteins by the human herpesviruses. Cell Div.4 , 1 (2009).
  • Hwang J , WinklerL, KalejtaRF. Ubiquitin-independent proteasomal degradation during oncogenic viral infections. Biochim. Biophys. Acta1816(2) , 147–157 (2011).
  • Hwang J , KalejtaRF. Proteasome-dependent, ubiquitin-independent degradation of Daxx by the viral pp71 protein in human cytomegalovirus-infected cells. Virology367(2) , 334–338 (2007).
  • Schulman BA , HarperJW. Ubiquitin-like protein activation by E1 enzymes: the apex for downstream signalling pathways. Nat. Rev. Mol. Cell. Biol.10(5) , 319–331 (2009).
  • Salvat C , AcquavivaC, ScheffnerM, RobbinsI, PiechaczykM, Jariel-EncontreI. Molecular characterization of the thermosensitive E1 ubiquitin-activating enzyme cell mutant A31N-ts20. Requirements upon different levels of E1 for the ubiquitination/degradation of the various protein substrates in vivo. Eur. J. Biochem.267(12) , 3712–3722 (2000).
  • Salsman J , JagannathanM, PaladinoP et al. Proteomic profiling of the human cytomegalovirus UL35 gene products reveals a role for UL35 in the DNA repair response. J. Virol. 86(2) , 806–820 (2012).
  • Tavalai N , PapiorP, RechterS, StammingerT. Nuclear domain 10 components promyelocytic leukemia protein and hDaxx independently contribute to an intrinsic antiviral defense against human cytomegalovirus infection. J. Virol.82(1) , 126–137 (2008).
  • Wethkamp N , HanenbergH, FunkeS et al. Daxx-beta and Daxx-gamma, two novel splice variants of the transcriptional co-repressor Daxx. J. Biol. Chem. 286(22) , 19576–19588 (2011).
  • Powers C , DefilippisV, MalouliD, FruhK. Cytomegalovirus immune evasion. Curr. Top. Microbiol. Immunol.325 , 333–359 (2008).
  • Neefjes J , JongsmaML, PaulP, BakkeO. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat. Rev. Immunol.11(12) , 823–836 (2011).
  • Lemmermann NA , BohmV, HoltappelsR, ReddehaseMJ. In vivo impact of cytomegalovirus evasion of CD8 T-cell immunity: facts and thoughts based on murine models. Virus Res.157(2) , 161–174 (2011).
  • Trgovcich J , CebullaC, ZimmermanP, SedmakDD. Human cytomegalovirus protein pp71 disrupts major histocompatibility complex class I cell surface expression. J. Virol.80(2) , 951–963 (2006).
  • Das S , PellettPE. Spatial relationships between markers for secretory and endosomal machinery in human cytomegalovirus-infected cells versus those in uninfected cells. J. Virol.85(12) , 5864–5879 (2011).
  • Sanchez V , GreisKD, SztulE, BrittWJ. Accumulation of virion tegument and envelope proteins in a stable cytoplasmic compartment during human cytomegalovirus replication: characterization of a potential site of virus assembly. J. Virol.74(2) , 975–986 (2000).
  • Van Domselaar R , PhilippenLE, QuadirR, WiertzEJ, KummerJA, BovenschenN. Noncytotoxic inhibition of cytomegalovirus replication through NK cell protease granzyme M-mediated cleavage of viral phosphoprotein 71. J. Immunol.185(12) , 7605–7613 (2010).
  • Chowdhury D , LiebermanJ. Death by a thousand cuts: granzyme pathways of programmed cell death. Annu. Rev. Immunol.26 , 389–420 (2008).
  • Knickelbein JE , KhannaKM, YeeMB, BatyCJ, KinchingtonPR, HendricksRL. Noncytotoxic lytic granule-mediated CD8+ T cell inhibition of HSV-1 reactivation from neuronal latency. Science322(5899) , 268–271 (2008).
  • Tavalai N , StammingerT. Intrinsic cellular defense mechanisms targeting human cytomegalovirus. Virus Res.157(2) , 128–133 (2011).
  • Zydek M , UeckerR, TavalaiN, StammingerT, HagemeierC, WiebuschL. General blockade of human cytomegalovirus immediate–early mRNA expression in the S/G2 phase by a nuclear, Daxx- and PML-independent mechanism. J. Gen. Virol.92(Pt 12) , 2757–2769 (2011).
  • Sinclair J . Chromatin structure regulates human cytomegalovirus gene expression during latency, reactivation and lytic infection. Biochim. Biophys. Acta1799(3–4) , 286–295 (2010).
  • Soroceanu L , CobbsCS. Is HCMV a tumor promoter? Virus Res.157(2) , 193–203 (2011).
  • Noriega V , RedmannV, GardnerT, TortorellaD. Diverse immune evasion strategies by human cytomegalovirus. Immunol. Res. doi:10.1007/s12026-012-8304-8 (2012) (Epub ahead of print).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.