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Live or let die: manipulation of cellular suicide programs by murine cytomegalovirus

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Abstract

Cytomegaloviruses (CMVs) are large double-stranded DNA viruses that replicate slowly and cause life-long persisting infections in their hosts. To achieve this, the CMVs had to evolve numerous countermeasures against innate and adaptive immune responses. Induction of programmed cell death is one important host defense mechanism against intracellular pathogens such as viruses. For a multicellular organism, it is advantageous to let infected cells die in order to thwart viral replication and dissemination. For a virus, by contrast, it is better to inhibit cell death and keep infected cells alive until the viral replication cycle has been completed. As a matter of fact, the CMVs encode a number of proteins devoted to interfering with different forms of programmed cell death: apoptosis and necroptosis. In this review, we summarize the known functions of the four best characterized cell death inhibitors of murine cytomegalovirus (MCMV), which are encoded by open reading frames, M36, m38.5, m41.1, and M45. The viral proteins interact with key molecules within different cell death pathways, namely caspase-8, Bax, Bak, and RIP1/RIP3. In addition, we discuss which events during MCMV infection might trigger apoptosis or necrosis and how MCMV’s countermeasures compare to those of other herpesviruses. Since both, MCMV and its natural host, are amenable to genetic manipulation, the mouse model for CMV infection provides a particularly suitable system to study mechanisms of cell death induction and inhibition.

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References

  1. Cannon MJ, Schmid DS, Hyde TB (2010) Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol 20(4):202–213

    Article  PubMed  Google Scholar 

  2. Cheung TW, Teich SA (1999) Cytomegalovirus infection in patients with HIV infection. Mt Sinai J Med 66(2):113–124

    PubMed  CAS  Google Scholar 

  3. Steininger C (2007) Clinical relevance of cytomegalovirus infection in patients with disorders of the immune system. Clin Microbiol Infect 13(10):953–963

    Article  PubMed  CAS  Google Scholar 

  4. Grosse SD, Ross DS, Dollard SC (2008) Congenital cytomegalovirus (CMV) infection as a cause of permanent bilateral hearing loss: a quantitative assessment. J Clin Virol 41(2):57–62

    Article  PubMed  Google Scholar 

  5. Sung H, Schleiss MR (2010) Update on the current status of cytomegalovirus vaccines. Expert Rev Vaccines 9(11):1303–1314

    Article  PubMed  CAS  Google Scholar 

  6. Lurain NS, Chou S (2010) Antiviral drug resistance of human cytomegalovirus. Clin Microbiol Rev 23(4):689–712

    Article  PubMed  CAS  Google Scholar 

  7. Hudson JB (1979) The murine cytomegalovirus as a model for the study of viral pathogenesis and persistent infections. Arch Virol 62(1):1–29

    Article  PubMed  CAS  Google Scholar 

  8. Sinclair J, Sissons P (2006) Latency and reactivation of human cytomegalovirus. J Gen Virol 87(Pt 7):1763–1779

    Article  PubMed  CAS  Google Scholar 

  9. Galluzzi L et al (2012) Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ 19(1):107–120

    Article  PubMed  CAS  Google Scholar 

  10. Kroemer G et al (2009) Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ 16(1):3–11

    Article  PubMed  CAS  Google Scholar 

  11. Barnhart BC, Alappat EC, Peter ME (2003) The CD95 type I/type II model. Semin Immunol 15(3):185–193

    Article  PubMed  CAS  Google Scholar 

  12. Scaffidi C et al (1998) Two CD95 (APO-1/Fas) signaling pathways. EMBO J 17(6):1675–1687

    Article  PubMed  CAS  Google Scholar 

  13. Thorburn A (2004) Death receptor-induced cell killing. Cell Signal 16(2):139–144

    Article  PubMed  CAS  Google Scholar 

  14. Skaletskaya A et al (2001) A cytomegalovirus-encoded inhibitor of apoptosis that suppresses caspase-8 activation. Proc Natl Acad Sci USA 98(14):7829–7834

    Article  PubMed  CAS  Google Scholar 

  15. Menard C et al (2003) Role of murine cytomegalovirus US22 gene family members in replication in macrophages. J Virol 77(10):5557–5570

    Article  PubMed  CAS  Google Scholar 

  16. McCormick AL et al (2003) Differential function and expression of the viral inhibitor of caspase 8-induced apoptosis (vICA) and the viral mitochondria-localized inhibitor of apoptosis (vMIA) cell death suppressors conserved in primate and rodent cytomegaloviruses. Virology 316(2):221–233

    Article  PubMed  CAS  Google Scholar 

  17. Cicin-Sain L et al (2008) Dominant-negative FADD rescues the in vivo fitness of a cytomegalovirus lacking an antiapoptotic viral gene. J Virol 82(5):2056–2064

    Article  PubMed  CAS  Google Scholar 

  18. Norris KL, Youle RJ (2008) Cytomegalovirus proteins vMIA and m38.5 link mitochondrial morphogenesis to Bcl-2 family proteins. J Virol 82(13):6232–6243

    Article  PubMed  CAS  Google Scholar 

  19. Jurak I et al (2008) Murine cytomegalovirus m38.5 protein inhibits Bax-mediated cell death. J Virol 82(10):4812–4822

    Article  PubMed  CAS  Google Scholar 

  20. Arnoult D et al (2008) The murine cytomegalovirus cell death suppressor m38.5 binds Bax and blocks Bax-mediated mitochondrial outer membrane permeabilization. Apoptosis 13(9):1100–1110

    Article  PubMed  CAS  Google Scholar 

  21. Manzur M et al (2009) Virally mediated inhibition of Bax in leukocytes promotes dissemination of murine cytomegalovirus. Cell Death Differ 16(2):312–320

    Article  PubMed  CAS  Google Scholar 

  22. Cam M et al (2010) Cytomegaloviruses inhibit Bak- and Bax-mediated apoptosis with two separate viral proteins. Cell Death Differ 17(4):655–665

    Article  PubMed  CAS  Google Scholar 

  23. McCormick AL et al (2005) Mitochondrial cell death suppressors carried by human and murine cytomegalovirus confer resistance to proteasome inhibitor-induced apoptosis. J Virol 79(19):12205–12217

    Article  PubMed  CAS  Google Scholar 

  24. Goldmacher VS et al (1999) A cytomegalovirus-encoded mitochondria-localized inhibitor of apoptosis structurally unrelated to Bcl-2. Proc Natl Acad Sci USA 96(22):12536–12541

    Article  PubMed  CAS  Google Scholar 

  25. Goldmacher VS (2005) Cell death suppression by cytomegaloviruses. Apoptosis 10(2):251–265

    Article  PubMed  CAS  Google Scholar 

  26. Arnoult D et al (2004) Cytomegalovirus cell death suppressor vMIA blocks Bax- but not Bak-mediated apoptosis by binding and sequestering Bax at mitochondria. Proc Nat Acad Sci USA 101(21):7988–7993

    Article  PubMed  CAS  Google Scholar 

  27. Poncet D et al (2004) An anti-apoptotic viral protein that recruits Bax to mitochondria. J Biol Chem 279(21):22605–22614

    Article  PubMed  CAS  Google Scholar 

  28. Festjens N, Vanden Berghe T, Vandenabeele P (2006) Necrosis, a well-orchestrated form of cell demise: signalling cascades, important mediators and concomitant immune response. Biochim Biophys Acta 1757(9–10):1371–1387

    PubMed  CAS  Google Scholar 

  29. Vandenabeele P et al (2010) Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol 11(10):700–714

    Article  PubMed  CAS  Google Scholar 

  30. Vandenabeele P et al (2010) The role of the kinases RIP1 and RIP3 in TNF-induced necrosis. Sci Signal 3(115):e4

    Article  CAS  Google Scholar 

  31. Goossens V et al (1999) Regulation of tumor necrosis factor-induced, mitochondria- and reactive oxygen species-dependent cell death by the electron flux through the electron transport chain complex I. Antioxid Redox Signal 1(3):285–295

    Article  PubMed  CAS  Google Scholar 

  32. Zhang DW et al (2009) RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 325(5938):332–336

    Article  PubMed  CAS  Google Scholar 

  33. Feoktistova M et al (2011) cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms. Mol Cell 43(3):449–463

    Article  PubMed  CAS  Google Scholar 

  34. Kaiser WJ, Offermann MK (2005) Apoptosis induced by the toll-like receptor adaptor TRIF is dependent on its receptor interacting protein homotypic interaction motif. J Immunol 174(8):4942–4952

    PubMed  CAS  Google Scholar 

  35. Rebsamen M et al (2009) DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB. EMBO Rep 10(8):916–922

    Article  PubMed  CAS  Google Scholar 

  36. Upton J, K.W.a.M. E. (2012) DAI/ZBP1/DLM-1 Complexes with RIP3 to mediate virus-induced programmed necrosis that is targeted by murine cytomegalovirus vIRA. Cell Host Microbe 11(3)

  37. Brune W et al (2001) A ribonucleotide reductase homolog of cytomegalovirus and endothelial cell tropism. Science 291(5502):303–305

    Article  PubMed  CAS  Google Scholar 

  38. Lembo D et al (2004) The ribonucleotide reductase R1 homolog of murine cytomegalovirus is not a functional enzyme subunit but is required for pathogenesis. J Virol 78(8):4278–4288

    Article  PubMed  CAS  Google Scholar 

  39. Mack C et al (2008) Inhibition of proinflammatory and innate immune signaling pathways by a cytomegalovirus RIP1-interacting protein. Proc Natl Acad Sci US A 105(8):3094–3099

    Article  CAS  Google Scholar 

  40. Upton JW, Kaiser WJ, Mocarski ES (2008) Cytomegalovirus M45 cell death suppression requires receptor-interacting protein (RIP) homotypic interaction motif (RHIM)-dependent interaction with RIP1. J Biol Chem 283(25):16966–16970

    Article  PubMed  CAS  Google Scholar 

  41. Upton JW, Kaiser WJ, Mocarski ES (2010) Virus inhibition of RIP3-dependent necrosis. Cell Host Microbe 7(4):302–313

    Article  PubMed  CAS  Google Scholar 

  42. Fliss PM et al (2012) Viral mediated redirection of NEMO/IKKgamma to autophagosomes curtails the inflammatory cascade. PLoS Pathog 8(2):e1002517

    Article  PubMed  CAS  Google Scholar 

  43. Dutta J et al (2006) Current insights into the regulation of programmed cell death by NF-kappaB. Oncogene 25(51):6800–6816

    Article  PubMed  CAS  Google Scholar 

  44. Pichlmair A, Reis e Sousa C (2007) Innate recognition of viruses. Immunity 27(3):370–383

    Article  PubMed  CAS  Google Scholar 

  45. Maher SG et al (2007) Interferon: cellular executioner or white knight? Curr Med Chem 14(12):1279–1289

    Article  PubMed  CAS  Google Scholar 

  46. Brandstadter JD, Yang Y (2011) Natural killer cell responses to viral infection. J Innate Immun 3(3):274–279

    Article  PubMed  CAS  Google Scholar 

  47. Zahringer U et al (2008) TLR2—promiscuous or specific? A critical re-evaluation of a receptor expressing apparent broad specificity. Immunobiology 213(3–4):205–224

    Article  PubMed  CAS  Google Scholar 

  48. Boehme KW, Guerrero M, Compton T (2006) Human cytomegalovirus envelope glycoproteins B and H are necessary for TLR2 activation in permissive cells. J Immunol 177(10):7094–7102

    PubMed  CAS  Google Scholar 

  49. Szomolanyi-Tsuda E et al (2006) Role for TLR2 in NK cell-mediated control of murine cytomegalovirus in vivo. J Virol 80(9):4286–4291

    Article  PubMed  CAS  Google Scholar 

  50. Aliprantis AO et al (2000) The apoptotic signaling pathway activated by Toll-like receptor-2. EMBO J 19(13):3325–3336

    Article  PubMed  CAS  Google Scholar 

  51. Aravalli RN, Hu S, Lokensgard JR (2007) Toll-like receptor 2 signaling is a mediator of apoptosis in herpes simplex virus-infected microglia. J Neuroinflammation 4:11

    Article  PubMed  Google Scholar 

  52. He S et al (2011) Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway. Proc Natl Acad Sci USA 108(50):20054–20059

    Article  PubMed  CAS  Google Scholar 

  53. Tabeta K et al (2004) Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc Natl Acad Sci USA 101(10):3516–3521

    Article  PubMed  CAS  Google Scholar 

  54. Edelmann KH et al (2004) Does Toll-like receptor 3 play a biological role in virus infections? Virology 322(2):231–238

    Article  PubMed  CAS  Google Scholar 

  55. Takaoka A et al (2007) DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature 448(7152):501–505

    Article  PubMed  CAS  Google Scholar 

  56. Kaiser WJ, Upton JW, Mocarski ES (2008) Receptor-interacting protein homotypic interaction motif-dependent control of NF-kappa B activation via the DNA-dependent activator of IFN regulatory factors. J Immunol 181(9):6427–6434

    PubMed  CAS  Google Scholar 

  57. Wu J, Fernandes-Alnemri T, Alnemri ES (2010) Involvement of the AIM2, NLRC4, and NLRP3 inflammasomes in caspase-1 activation by Listeria monocytogenes. J Clin Immunol 30(5):693–702

    Article  PubMed  CAS  Google Scholar 

  58. Miao EA, Rajan JV, Aderem A (2011) Caspase-1-induced pyroptotic cell death. Immunol Rev 243(1):206–214

    Article  PubMed  CAS  Google Scholar 

  59. Fernandes-Alnemri T et al (2009) AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458(7237):509–513

    Article  PubMed  CAS  Google Scholar 

  60. Bergsbaken T, Fink SL, Cookson BT (2009) Pyroptosis: host cell death and inflammation. Nat Rev Microbiol 7(2):99–109

    Article  PubMed  CAS  Google Scholar 

  61. Rathinam VA et al (2010) The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat Immunol 11(5):395–402

    Article  PubMed  CAS  Google Scholar 

  62. Clemens MJ, Elia A (1997) The double-stranded RNA-dependent protein kinase PKR: structure and function. J Interferon Cytokine Res 17(9):503–524

    Article  PubMed  CAS  Google Scholar 

  63. Gil J, Esteban M (2000) Induction of apoptosis by the dsRNA-dependent protein kinase (PKR): mechanism of action. Apoptosis 5(2):107–114

    Article  PubMed  CAS  Google Scholar 

  64. Valchanova RS et al (2006) Murine cytomegalovirus m142 and m143 are both required to block protein kinase R-mediated shutdown of protein synthesis. J Virol 80(20):10181–10190

    Article  PubMed  CAS  Google Scholar 

  65. Budt M et al (2009) Specific inhibition of the PKR-mediated antiviral response by the murine cytomegalovirus proteins m142 and m143. J Virol 83(3):1260–1270

    Article  PubMed  CAS  Google Scholar 

  66. Child SJ, Geballe AP (2009) Binding and relocalization of protein kinase R by murine cytomegalovirus. J Virol 83(4):1790–1799

    Article  PubMed  CAS  Google Scholar 

  67. Szegezdi E et al (2006) Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep 7(9):880–885

    Article  PubMed  CAS  Google Scholar 

  68. Wek RC, Jiang HY, Anthony TG (2006) Coping with stress: eIF2 kinases and translational control. Biochem Soc Trans 34(Pt 1):7–11

    PubMed  CAS  Google Scholar 

  69. Isler JA, Skalet AH, Alwine JC (2005) Human cytomegalovirus infection activates and regulates the unfolded protein response. J Virol 79(11):6890–6899

    Article  PubMed  CAS  Google Scholar 

  70. Xuan B et al (2009) Human cytomegalovirus protein pUL38 induces ATF4 expression, inhibits persistent JNK phosphorylation, and suppresses endoplasmic reticulum stress-induced cell death. J Virol 83(8):3463–3474

    Article  PubMed  CAS  Google Scholar 

  71. Qian Z et al (2012) Murine cytomegalovirus targets transcription factor ATF4 to exploit the unfolded-protein response. J Virol 86(12):6712–6723

    Article  PubMed  CAS  Google Scholar 

  72. Shiloh Y (2006) The ATM-mediated DNA-damage response: taking shape. Trends Biochem Sci 31(7):402–410

    Article  PubMed  CAS  Google Scholar 

  73. Shieh SY et al (2000) The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes Dev 14(3):289–300

    PubMed  CAS  Google Scholar 

  74. Canman CE et al (1998) Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science 281(5383):1677–1679

    Article  PubMed  CAS  Google Scholar 

  75. Yang Y et al (2011) A cytosolic ATM/NEMO/RIP1 complex recruits TAK1 to mediate the NF-kappaB and p38 mitogen-activated protein kinase (MAPK)/MAPK-activated protein 2 responses to DNA damage. Mol Cell Biol 31(14):2774–2786

    Article  PubMed  CAS  Google Scholar 

  76. Bock FJ et al (2012) P53-induced protein with a death domain (PIDD): master of puppets? Oncogene

  77. Janssens S, Tinel A (2012) The PIDDosome, DNA-damage-induced apoptosis and beyond. Cell Death Differ 19(1):13–20

    Article  PubMed  CAS  Google Scholar 

  78. Gaspar M, Shenk T (2006) Human cytomegalovirus inhibits a DNA damage response by mislocalizing checkpoint proteins. Proc Natl Acad Sci USA 103(8):2821–2826

    Article  PubMed  CAS  Google Scholar 

  79. Shen YH et al (2004) Human cytomegalovirus causes endothelial injury through the ataxia telangiectasia mutant and p53 DNA damage signaling pathways. Circ Res 94(10):1310–1317

    Article  PubMed  CAS  Google Scholar 

  80. Dufour F et al (2011) The ribonucleotide reductase R1 subunits of herpes simplex virus types 1 and 2 protect cells against TNFalpha- and FasL-induced apoptosis by interacting with caspase-8. Apoptosis 16(3):256–271

    Article  PubMed  CAS  Google Scholar 

  81. Dufour F et al (2011) The ribonucleotide reductase R1 subunits of herpes simplex virus 1 and 2 protect cells against poly(I. C)-induced apoptosis. J Virol 85(17):8689–8701

    Article  PubMed  CAS  Google Scholar 

  82. Thome M et al (1997) Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature 386(6624):517–521

    Article  PubMed  CAS  Google Scholar 

  83. Brooks C et al (2007) Bak regulates mitochondrial morphology and pathology during apoptosis by interacting with mitofusins. Proc Natl Acad Sci USA 104(28):11649–11654

    Article  PubMed  CAS  Google Scholar 

  84. Cartron PF et al (2003) Nonredundant role of Bax and Bak in Bid-mediated apoptosis. Mol Cell Biol 23(13):4701–4712

    Article  PubMed  CAS  Google Scholar 

  85. Neise D et al (2008) Activation of the mitochondrial death pathway is commonly mediated by a preferential engagement of Bak. Oncogene 27(10):1387–1396

    Article  PubMed  CAS  Google Scholar 

  86. Karbowski M et al (2006) Role of Bax and Bak in mitochondrial morphogenesis. Nature 443(7112):658–662

    Article  PubMed  CAS  Google Scholar 

  87. Cheng EH et al (1997) A Bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with Bax or Bak. Proc Natl Acad Sci USA 94(2):690–694

    Article  PubMed  CAS  Google Scholar 

  88. Cheng G, Feng Z, He B (2005) Herpes simplex virus 1 infection activates the endoplasmic reticulum resident kinase PERK and mediates eIF-2alpha dephosphorylation by the gamma(1)34.5 protein. J Virol 79(3):1379–1388

    Article  PubMed  CAS  Google Scholar 

  89. Carpenter JE et al (2011) Autophagosome formation during varicella-zoster virus infection following endoplasmic reticulum stress and the unfolded protein response. J Virol 85(18):9414–9424

    Article  PubMed  CAS  Google Scholar 

  90. Qian Z et al (2011) The human cytomegalovirus protein pUL38 suppresses endoplasmic reticulum stress-mediated cell death independently of its ability to induce mTORC1 activation. J Virol 85(17):9103–9113

    Article  PubMed  CAS  Google Scholar 

  91. Brune W (2011) Inhibition of programmed cell death by cytomegaloviruses. Virus Res 157(2):144–150

    Article  PubMed  CAS  Google Scholar 

  92. Hicks SW, Machamer CE (2005) Golgi structure in stress sensing and apoptosis. Biochim Biophys Acta 1744(3):406–414

    Article  PubMed  CAS  Google Scholar 

  93. Lane JD et al (2002) Caspase-mediated cleavage of the stacking protein GRASP65 is required for Golgi fragmentation during apoptosis. J Cell Biol 156(3):495–509

    Article  PubMed  CAS  Google Scholar 

  94. Walker A et al (2004) Golgi fragmentation during Fas-mediated apoptosis is associated with the rapid loss of GM130. Biochem Biophys Res Commun 316(1):6–11

    Article  PubMed  CAS  Google Scholar 

  95. Mancini M et al (2000) Caspase-2 is localized at the Golgi complex and cleaves golgin-160 during apoptosis. J Cell Biol 149(3):603–612

    Article  PubMed  CAS  Google Scholar 

  96. Brune W, Nevels M, Shenk T (2003) Murine cytomegalovirus m41 open reading frame encodes a Golgi-localized antiapoptotic protein. J Virol 77(21):11633–11643

    Article  PubMed  CAS  Google Scholar 

  97. de Mattia F et al (2009) Human Golgi antiapoptotic protein modulates intracellular calcium fluxes. Mol Biol Cell 20(16):3638–3645

    Article  PubMed  CAS  Google Scholar 

  98. Gubser C et al (2007) A new inhibitor of apoptosis from vaccinia virus and eukaryotes. PLoS Pathog 3(2):e17

    Article  PubMed  CAS  Google Scholar 

  99. Nikitin PA et al (2010) An ATM/Chk2-mediated DNA damage-responsive signaling pathway suppresses Epstein-Barr virus transformation of primary human B cells. Cell Host Microbe 8(6):510–522

    Article  PubMed  CAS  Google Scholar 

  100. Wilkinson DE, Weller SK (2004) Recruitment of cellular recombination and repair proteins to sites of herpes simplex virus type 1 DNA replication is dependent on the composition of viral proteins within prereplicative sites and correlates with the induction of the DNA damage response. J Virol 78(9):4783–4796

    Article  PubMed  CAS  Google Scholar 

  101. Luo MH et al (2007) Human cytomegalovirus disrupts both ataxia telangiectasia mutated protein (ATM)- and ATM-Rad3-related kinase-mediated DNA damage responses during lytic infection. J Virol 81(4):1934–1950

    Article  PubMed  CAS  Google Scholar 

  102. Tuddenham L, Pfeffer S (2011) Roles and regulation of microRNAs in cytomegalovirus infection. Biochim Biophys Acta 1809(11–12):613–622

    PubMed  CAS  Google Scholar 

  103. Suffert G et al (2011) Kaposi’s sarcoma herpesvirus microRNAs target caspase 3 and regulate apoptosis. PLoS Pathog 7(12):e1002405

    Article  PubMed  CAS  Google Scholar 

  104. Reeves MB et al (2007) Complex I binding by a virally encoded RNA regulates mitochondria-induced cell death. Science 316(5829):1345–1348

    Article  PubMed  CAS  Google Scholar 

  105. Brune W, Hengel H, Koszinowski UH (2001) A mouse model for cytomegalovirus infection. Curr Protoc Immunol Chapter 19, Unit 19 7

  106. Guan C et al (2010) A review of current large-scale mouse knockout efforts. Genesis 48(2):73–85

    PubMed  CAS  Google Scholar 

  107. Ruzsics Z, Koszinowski UH (2008) Mutagenesis of the cytomegalovirus genome. Curr Top Microbiol Immunol 325:41–61

    Google Scholar 

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Acknowledgments

The authors would like to thank Patricia Fliss for a critical reading of the manuscript. This work was supported by the German Research Foundation (BR 1730/3-1 to W.B.).

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The authors declare that they have no conflict of interest.

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  1. Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistr. 52, 20251, Hamburg, Germany

    Wiebke Handke, Eva Krause & Wolfram Brune

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  1. Wiebke Handke
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  2. Eva Krause
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  3. Wolfram Brune
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Correspondence to Wolfram Brune.

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Wiebke Handke and Eva Krause contributed equally to this work.

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Handke, W., Krause, E. & Brune, W. Live or let die: manipulation of cellular suicide programs by murine cytomegalovirus. Med Microbiol Immunol 201, 475–486 (2012). https://doi.org/10.1007/s00430-012-0264-z

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