#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Host signaling and EGR1 transcriptional control of human cytomegalovirus replication and latency


Autoři: Jason Buehler aff001;  Ethan Carpenter aff001;  Sebastian Zeltzer aff001;  Suzu Igarashi aff001;  Michael Rak aff001;  Iliyana Mikell aff002;  Jay A. Nelson aff002;  Felicia Goodrum aff001
Působiště autorů: Bio5 Institute, University of Arizona, Tucson, Arizona, United States of America aff001;  Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America aff002;  Department of Immunobiology, University of Arizona, Tucson, Arizona, United States of America aff003
Vyšlo v časopise: Host signaling and EGR1 transcriptional control of human cytomegalovirus replication and latency. PLoS Pathog 15(11): e32767. doi:10.1371/journal.ppat.1008037
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008037

Souhrn

Sustained phosphotinositide3-kinase (PI3K) signaling is critical to the maintenance of alpha and beta herpesvirus latency. We have previously shown that the beta-herpesvirus, human cytomegalovirus (CMV), regulates epidermal growth factor receptor (EGFR), upstream of PI3K, to control states of latency and reactivation. How signaling downstream of EGFR is regulated and how this impacts CMV infection and latency is not fully understood. We demonstrate that CMV downregulates EGFR early in the productive infection, which blunts the activation of EGFR and its downstream pathways in response to stimuli. However, CMV infection sustains basal levels of EGFR and downstream pathway activity in the context of latency in CD34+ hematopoietic progenitor cells (HPCs). Inhibition of MEK/ERK, STAT or PI3K/AKT pathways downstream of EGFR increases viral reactivation from latently infected CD34+ HPCs, defining a role for these pathways in latency. We hypothesized that CMV modulation of EGFR signaling might impact viral transcription important to latency. Indeed, EGF-stimulation increased expression of the UL138 latency gene, but not immediate early or early viral genes, suggesting that EGFR signaling promotes latent gene expression. The early growth response-1 (EGR1) transcription factor is induced downstream of EGFR signaling through the MEK/ERK pathway and is important for the maintenance of hematopoietic stemness. We demonstrate that EGR1 binds the viral genome upstream of UL138 and is sufficient to promote UL138 expression. Further, disruption of EGR1 binding upstream of UL138 prevents the establishment of latency in CD34+ HPCs. Our results indicate a model whereby UL138 modulation of EGFR signaling feeds back to promote UL138 gene expression and suppression of replication for latency. By this mechanism, the virus has hardwired itself into host cell biology to sense and respond to changes in homeostatic host cell signaling.

Klíčová slova:

Cell differentiation – Cell signaling – EGFR signaling – Fibroblasts – Gene expression – Viral persistence and latency – Viral replication – Virus effects on host gene expression


Zdroje

1. Mendelson M, Monard S, Sissons P, Sinclair J. Detection of endogenous human cytomegalovirus in CD34+ bone marrow progenitors. J Gen Virol. 1996;77(12):3099–102.

2. Cheng S, Caviness K, Buehler J, Smithey M, Nikolich-Zugich J, Goodrum F. Transcriptome-wide characterization of human cytomegalovirus in natural infection and experimental latency. Proc Natl Acad Sci U S A. 2017;114(49):E10586–e95. Epub 2017/11/22. doi: 10.1073/pnas.1710522114 29158406; PubMed Central PMCID: PMC5724264.

3. Shnayder M, Nachshon A, Krishna B, Poole E, Boshkov A, Binyamin A, et al. Defining the Transcriptional Landscape during Cytomegalovirus Latency with Single-Cell RNA Sequencing. mBio. 2018;9(2):e00013–18. doi: 10.1128/mBio.00013-18 29535194

4. Boeckh M, Geballe AP. Cytomegalovirus: pathogen, paradigm, and puzzle. The Journal of Clinical Investigation. 2011;121(5):1673–80. doi: 10.1172/JCI45449 21659716

5. Ljungman P, Hakki M, Boeckh M. Cytomegalovirus in Hematopoietic Stem Cell Transplant Recipients. Hematology/oncology clinics of North America. 2011;25(1):151–69. doi: 10.1016/j.hoc.2010.11.011 21236396

6. Razonable RR, Humar A, Practice tAIDCo. Cytomegalovirus in Solid Organ Transplantation. American Journal of Transplantation. 2013;13(s4):93–106. doi: 10.1111/ajt.12103

7. Ljungman P, Engelhard D, Link H, Biron P, Brandt L, Brunet S, et al. Treatment of Interstitial Pneumonitis Due to Cytomegalovirus with Ganciclovir and Intravenous Immune Globulin: Experience of European Bone Marrow Transplant Group. Clinical Infectious Diseases. 1992;14(4):831–5. doi: 10.1093/clinids/14.4.831 1315585

8. Kuo CP, Wu CL, Ho HT, Chen CG, Liu SI, Lu YT. Detection of cytomegalovirus reactivation in cancer patients receiving chemotherapy. Clinical Microbiology and Infection. 2008;14(3):221–7. doi: 10.1111/j.1469-0691.2007.01895.x 18070129

9. Collins-McMillen D, Kim JH, Nogalski MT, Stevenson EV, Chan GC, Caskey JR, et al. Human Cytomegalovirus Promotes Survival of Infected Monocytes via a Distinct Temporal Regulation of Cellular Bcl-2 Family Proteins. Journal of Virology. 2016;90(5):2356–71. doi: 10.1128/jvi.01994-15 26676786

10. Chan G, Nogalski MT, Bentz GL, Smith MS, Parmater A, Yurochko AD. PI3K-Dependent Upregulation of Mcl-1 by Human Cytomegalovirus Is Mediated by Epidermal Growth Factor Receptor and Inhibits Apoptosis in Short-Lived Monocytes. The Journal of Immunology. 2010;184(6):3213–22. doi: 10.4049/jimmunol.0903025 20173022

11. Collins-McMillen D, Stevenson EV, Kim JH, Lee B-J, Cieply SJ, Nogalski MT, et al. Human Cytomegalovirus Utilizes a Nontraditional Signal Transducer and Activator of Transcription 1 Activation Cascade via Signaling through Epidermal Growth Factor Receptor and Integrins To Efficiently Promote the Motility, Differentiation, and Polarization of Infected Monocytes. Journal of Virology. 2017;91(24). doi: 10.1128/jvi.00622-17 29021395

12. Campadelli-Fiume G, Collins-McMillen D, Gianni T, Yurochko AD. Integrins as Herpesvirus Receptors and Mediators of the Host Signalosome. Annual Review of Virology. 2016;3(1):215–36. doi: 10.1146/annurev-virology-110615-035618 27501260.

13. Collins-McMillen D, Buehler J, Peppenelli M, Goodrum F. Molecular Determinants and the Regulation of Human Cytomegalovirus Latency and Reactivation. Viruses. 2018;10(8):444. doi: 10.3390/v10080444 30127257

14. Goodrum F. Human Cytomegalovirus Latency: Approaching the Gordian Knot. Annu Rev Virol. 2016;3(1):333–57. Epub 2016/08/09. doi: 10.1146/annurev-virology-110615-042422 27501258.

15. Buehler J, Zeltzer S, Reitsma J, Petrucelli A, Umashankar M, Rak M, et al. Opposing Regulation of the EGF Receptor: A Molecular Switch Controlling Cytomegalovirus Latency and Replication. PLoS pathogens. 2016;12(5):e1005655. doi: 10.1371/journal.ppat.1005655 27218650

16. Kim JH, Collins-McMillen D, Buehler JC, Goodrum FD, Yurochko AD. Human Cytomegalovirus Requires Epidermal Growth Factor Receptor Signaling To Enter and Initiate the Early Steps in the Establishment of Latency in CD34+ Human Progenitor Cells. Journal of Virology. 2017;91(5). doi: 10.1128/jvi.01206-16 27974567

17. Umashankar M, Rak M, Bughio F, Zagallo P, Caviness K, Goodrum FD. Antagonistic determinants controlling replicative and latent states of human cytomegalovirus infection. J Virol. 2014;88(11):5987–6002. doi: 10.1128/JVI.03506-13 24623432.

18. Rak MA, Buehler J, Zeltzer S, Reitsma J, Molina B, Terhune S, et al. Human Cytomegalovirus UL135 Interacts with Host Adaptor Proteins To Regulate Epidermal Growth Factor Receptor and Reactivation from Latency. Journal of Virology. 2018;92(20):e00919–18. doi: 10.1128/JVI.00919-18 30089695

19. Min IM, Pietramaggiori G, Kim FS, Passegue E, Stevenson KE, Wagers AJ. The transcription factor EGR1 controls both the proliferation and localization of hematopoietic stem cells. Cell Stem Cell. 2008;2(4):380–91. doi: 10.1016/j.stem.2008.01.015 18397757.

20. Liu C, Yao J, de Belle I, Huang RP, Adamson E, Mercola D. The transcription factor EGR-1 suppresses transformation of human fibrosarcoma HT1080 cells by coordinated induction of transforming growth factor-beta1, fibronectin, and plasminogen activator inhibitor-1. The Journal of biological chemistry. 1999;274(7):4400–11. Epub 1999/02/06. doi: 10.1074/jbc.274.7.4400 9933644.

21. Krishnaraju K, Hoffman B, Liebermann DA. Early growth response gene 1 stimulates development of hematopoietic progenitor cells along the macrophage lineage at the expense of the granulocyte and erythroid lineages. Blood. 2001;97(5):1298–305. doi: 10.1182/blood.v97.5.1298 11222373.

22. von Laer D, Meyer-Koenig U, Serr A, Finke J, Kanz L, Fauser A, et al. Detection of cytomegalovirus DNA in CD34+ cells from blood and bone marrow. Blood. 1995;86(11):4086–90. 7492764

23. Maciejewski J, Bruening E, Donahue R, Mocarski E, Young N, St Jeor S. Infection of hematopoietic progenitor cells by human cytomegalovirus. Blood. 1992;80(1):170–8. 1377049

24. Goodrum F, Jordan CT, Terhune SS, High K, Shenk T. Differential outcomes of human cytomegalovirus infection in primitive hematopoietic cell subpopulations. Blood. 2004;104(3):687–95. Epub 2004/04/20. doi: 10.1182/blood-2003-12-4344 15090458.

25. Petrucelli A, Rak M, Grainger L, Goodrum F. Characterization of a Novel Golgi-localized Latency Determinant Encoded by Human Cytomegalovirus. J Virol. 2009;83(11):5615–29. Epub 2009/03/20. JVI.01989-08 [pii] doi: 10.1128/JVI.01989-08 19297488.

26. Umashankar M, Petrucelli A, Cicchini L, Caposio P, Kreklywich CN, Rak M, et al. A novel human cytomegalovirus locus modulates cell type-specific outcomes of infection. PLoS pathogens. 2011;7(12):e1002444. Epub 2012/01/14. doi: 10.1371/journal.ppat.1002444 22241980; PubMed Central PMCID: PMC3248471.

27. Fairley JA, Baillie J, Bain M, Sinclair JH. Human cytomegalovirus infection inhibits epidermal growth factor (EGF) signalling by targeting EGF receptors. Journal of General Virology. 2002;83(11):2803–10.

28. Jafferji I, Bain M, King C, Sinclair JH. Inhibition of epidermal growth factor receptor (EGFR) expression by human cytomegalovirus correlates with an increase in the expression and binding of Wilms' Tumour 1 protein to the EGFR promoter. Journal of General Virology. 2009;90(7):1569–74. doi: 10.1099/vir.0.009670–0

29. Peppenelli MA, Arend KC, Cojohari O, Moorman NJ, Chan GC. Human Cytomegalovirus Stimulates the Synthesis of Select Akt-Dependent Antiapoptotic Proteins during Viral Entry To Promote Survival of Infected Monocytes. Journal of Virology. 2016;90(6):3138–47. doi: 10.1128/JVI.02879-15 26739047

30. Chan G, Nogalski MT, Yurochko AD. Activation of EGFR on monocytes is required for human cytomegalovirus entry and mediates cellular motility. Proceedings of the National Academy of Sciences. 2009;106(52):22369–74. doi: 10.1073/pnas.0908787106 20018733

31. Johnson RA, Wang X, Ma X-L, Huong S-M, Huang E-S. Human Cytomegalovirus Up-Regulates the Phosphatidylinositol 3-Kinase (PI3-K) Pathway: Inhibition of PI3-K Activity Inhibits Viral Replication and Virus-Induced Signaling. Journal of Virology. 2001;75(13):6022–32. doi: 10.1128/JVI.75.13.6022-6032.2001 11390604

32. Reitsma JM, Sato H, Nevels M, Terhune SS, Paulus C. Human Cytomegalovirus IE1 Protein Disrupts Interleukin-6 Signaling by Sequestering STAT3 in the Nucleus. Journal of Virology. 2013;87(19):10763–76. doi: 10.1128/JVI.01197-13 23903834

33. Reitsma JM, Terhune SS. Inhibition of cellular STAT3 synergizes with the cytomegalovirus kinase inhibitor maribavir to disrupt infection. Antiviral Research. 2013;100(2):321–7. doi: 10.1016/j.antiviral.2013.09.011 24070820

34. Miller CL, Eaves CJ. Long-term culture-initiating cell assays for human and murine cells. Methods Mol Med. 2002;63:123–41. doi: 10.1385/1-59259-140-X:123 21437804.

35. Umashankar M, Goodrum F. Hematopoietic long-term culture (hLTC) for human cytomegalovirus latency and reactivation. Methods Mol Biol. 2014;1119:99–112. Epub 2014/03/19. doi: 10.1007/978-1-62703-788-4_7 24639220.

36. Waters KM, Liu T, Quesenberry RD, Willse AR, Bandyopadhyay S, Kathmann LE, et al. Network Analysis of Epidermal Growth Factor Signaling Using Integrated Genomic, Proteomic and Phosphorylation Data. PLOS ONE. 2012;7(3):e34515. doi: 10.1371/journal.pone.0034515 22479638

37. Broos S, Soete A, Hooghe B, Moran R, van Roy F, De Bleser P. PhysBinder: improving the prediction of transcription factor binding sites by flexible inclusion of biophysical properties. Nucleic Acids Research. 2013;41(W1):W531–W4. doi: 10.1093/nar/gkt288 23620286

38. Thiel G, Cibelli G. Regulation of life and death by the zinc finger transcription factor Egr-1. Journal of cellular physiology. 2002;193(3):287–92. doi: 10.1002/jcp.10178 12384981

39. Gineitis D, Treisman R. Differential Usage of Signal Transduction Pathways Defines Two Types of Serum Response Factor Target Gene. Journal of Biological Chemistry. 2001;276(27):24531–9. doi: 10.1074/jbc.M102678200 11342553

40. Cabodi S, Morello V, Masi A, Cicchi R, Broggio C, DiStefano P, et al. Convergence of integrins and EGF receptor signaling via PI3K/Akt/FoxO pathway in early gene Egr-1 expression. Journal of cellular physiology. 2009;218(2):294–303. doi: 10.1002/jcp.21603 18844239

41. Chakraborty S, Li L, Puliyappadamba VT, Guo G, Hatanpaa KJ, Mickey B, et al. Constitutive and ligand-induced EGFR signalling triggers distinct and mutually exclusive downstream signalling networks. Nature Communications. 2014;5:5811. doi: 10.1038/ncomms6811 https://www.nature.com/articles/ncomms6811#supplementary-information. 25503978

42. Grainger L, Cicchini L, Rak M, Petrucelli A, Fitzgerald KD, Semler BL, et al. Stress-Inducible Alternative Translation Initiation of Human Cytomegalovirus Latency Protein pUL138. J Virol. 2010;84(18):9472–86. doi: 10.1128/JVI.00855-10 20592073

43. Caviness K, Cicchini L, Rak M, Umashankar M, Goodrum F. Complex Expression of the UL136 Gene of Human Cytomegalovirus Results in Multiple Protein Isoforms with Unique Roles in Replication. Journal of Virology. 2014;88(24):14412–25. doi: 10.1128/JVI.02711-14 25297993

44. Stark TJ, Arnold JD, Spector DH, Yeo GW. High-Resolution Profiling and Analysis of Viral and Host Small RNAs during Human Cytomegalovirus Infection. Journal of Virology. 2012;86(1):226–35. doi: 10.1128/JVI.05903-11 22013051

45. Grey F, Antoniewicz A, Allen E, Saugstad J, McShea A, Carrington JC, et al. Identification and Characterization of Human Cytomegalovirus-Encoded MicroRNAs. Journal of Virology. 2005;79(18):12095–9. doi: 10.1128/JVI.79.18.12095-12099.2005 16140786

46. Mikell I, Crawford LB, Hancock M, Mitchell J, Buehler J, Goodrum F, et al. HCMV miR-US22 down -regulation of Egr-1 regulates CD34+ Hematopoietic Progenitor Cell Proliferation and Viral Reactivation. PLoS pathogens. 2019.

47. Englert C, Hou X, Maheswaran S, Bennett P, Ngwu C, Re GG, et al. WT1 suppresses synthesis of the epidermal growth factor receptor and induces apoptosis. The EMBO journal. 1995;14(19):4662–75. 7588596.

48. Ritchie MF, Yue C, Zhou Y, Houghton PJ, Soboloff J. Wilms tumor suppressor 1 (WT1) and early growth response 1 (EGR1) are regulators of STIM1 expression. The Journal of biological chemistry. 2010;285(14):10591–6. doi: 10.1074/jbc.M109.083493 20123987; PubMed Central PMCID: PMC2856267.

49. Bentz GL, Yurochko AD. Human CMV infection of endothelial cells induces an angiogenic response through viral binding to EGF receptor and beta1 and beta3 integrins. Proc Natl Acad Sci U S A. 2008;105(14):5531–6. Epub 2008/04/01. doi: 10.1073/pnas.0800037105 18375753; PubMed Central PMCID: PMC2291133.

50. Chan G, Nogalski MT, Stevenson EV, Yurochko AD. Human cytomegalovirus induction of a unique signalsome during viral entry into monocytes mediates distinct functional changes: a strategy for viral dissemination. J Leukoc Biol. 2012;92(4):743–52. Epub 2012/06/21. doi: 10.1189/jlb.0112040 22715139; PubMed Central PMCID: PMC3441319.

51. Avraham R, Yarden Y. Feedback regulation of EGFR signalling: decision making by early and delayed loops. Nature reviews Molecular cell biology. 2011;12(2):104–17. Epub 2011/01/22. doi: 10.1038/nrm3048 21252999.

52. Lindsey S, Langhans SA. Epidermal growth factor signaling in transformed cells. Int Rev Cell Mol Biol. 2015;314:1–41. doi: 10.1016/bs.ircmb.2014.10.001 25619714.

53. Lupberger J, Duong FH, Fofana I, Zona L, Xiao F, Thumann C, et al. Epidermal growth factor receptor signaling impairs the antiviral activity of interferon-alpha. Hepatology. 2013;58(4):1225–35. Epub 2013/03/23. doi: 10.1002/hep.26404 23519785.

54. Yamashita M, Chattopadhyay S, Fensterl V, Saikia P, Wetzel JL, Sen GC. Epidermal growth factor receptor is essential for Toll-like receptor 3 signaling. Science signaling. 2012;5(233):ra50. Epub 2012/07/20. doi: 10.1126/scisignal.2002581 22810896; PubMed Central PMCID: PMC3431157.

55. Ortega J, Li JY, Lee S, Tong D, Gu L, Li GM. Phosphorylation of PCNA by EGFR inhibits mismatch repair and promotes misincorporation during DNA synthesis. Proc Natl Acad Sci U S A. 2015;112(18):5667–72. doi: 10.1073/pnas.1417711112 25825764; PubMed Central PMCID: PMC4426468.

56. Nguyen HQ, Hoffman-Liebermann B, Liebermann DA. The zinc finger transcription factor Egr-1 is essential for and restricts differentiation along the macrophage lineage. Cell. 1993;72(2):197–209. doi: 10.1016/0092-8674(93)90660-i 7678779

57. Camarena V, Kobayashi M, Kim JY, Roehm P, Perez R, Gardner J, et al. Nature and Duration of Growth Factor Signaling through Receptor Tyrosine Kinases Regulates HSV-1 Latency in Neurons. Cell Host & Microbe. 2010;8(4):320–30. http://dx.doi.org/10.1016/j.chom.2010.09.007.

58. Cliffe Anna R, Arbuckle Jesse H, Vogel Jodi L, Geden Matthew J, Rothbart Scott B, Cusack Corey L, et al. Neuronal Stress Pathway Mediating a Histone Methyl/Phospho Switch Is Required for Herpes Simplex Virus Reactivation. Cell Host & Microbe. 2015;18(6):649–58. doi: 10.1016/j.chom.2015.11.007 26651941

59. Strunk U, Ramos DG, Saffran HA, Smiley JR. Role of Herpes simplex virus 1 VP11/12 tyrosine-based binding motifs for Src family kinases, p85, Grb2 and Shc in activation of the phosphoinositide 3-kinase-Akt pathway. Virology. 2016;498:31–5. doi: 10.1016/j.virol.2016.08.007 27543756

60. Chuluunbaatar U, Roller R, Mohr I. Suppression of Extracellular Signal-Regulated Kinase Activity in Herpes Simplex Virus 1-Infected Cells by the Us3 Protein Kinase. Journal of Virology. 2012;86(15):7771–6. doi: 10.1128/JVI.00622-12 22593153

61. Miller WE, Earp HS, Raab-Traub N. The Epstein-Barr virus latent membrane protein 1 induces expression of the epidermal growth factor receptor. J Virol. 1995;69(7):4390–8. 7769701; PubMed Central PMCID: PMC189180.

62. Miller WE, Mosialos G, Kieff E, Raab-Traub N. Epstein-Barr virus LMP1 induction of the epidermal growth factor receptor is mediated through a TRAF signaling pathway distinct from NF-kappaB activation. J Virol. 1997;71(1):586–94. 8985387; PubMed Central PMCID: PMC191088.

63. Kung C-P, Meckes DG, Raab-Traub N. Epstein-Barr Virus LMP1 Activates EGFR, STAT3, and ERK through Effects on PKCδ. Journal of Virology. 2011;85(9):4399–408. doi: 10.1128/JVI.01703-10 21307189

64. Morrison JA, Klingelhutz AJ, Raab-Traub N. Epstein-Barr virus latent membrane protein 2A activates beta-catenin signaling in epithelial cells. J Virol. 2003;77(22):12276–84. Epub 2003/10/29. doi: 10.1128/JVI.77.22.12276-12284.2003 14581564; PubMed Central PMCID: PMC254275.

65. Swart R, Ruf IK, Sample J, Longnecker R. Latent membrane protein 2A-mediated effects on the phosphatidylinositol 3-Kinase/Akt pathway. J Virol. 2000;74(22):10838–45. Epub 2000/10/24. doi: 10.1128/jvi.74.22.10838-10845.2000 11044134; PubMed Central PMCID: PMC110964.

66. Iwakiri D, Minamitani T, Samanta M. Epstein-Barr Virus Latent Membrane Protein 2A Contributes to Anoikis Resistance through ERK Activation. Journal of Virology. 2013;87(14):8227–34. doi: 10.1128/JVI.01089-13 23698301

67. Peng L, Wu TT, Tchieu JH, Feng J, Brown HJ, Li X, et al. Inhibition of the phosphatidylinositol 3-kinase-Akt pathway enhances gamma-2 herpesvirus lytic replication and facilitates reactivation from latency. The Journal of general virology. 2010;91(Pt 2):463–9. Epub 2009/10/30. doi: 10.1099/vir.0.015073-0 19864499; PubMed Central PMCID: PMC2888311.

68. Ford PW, Bryan BA, Dyson OF, Weidner DA, Chintalgattu V, Akula SM. Raf/MEK/ERK signalling triggers reactivation of Kaposi's sarcoma-associated herpesvirus latency. Journal of General Virology. 2006;87(5):1139–44. doi: 10.1099/vir.0.81628–0

69. Dyson OF, Traylen CM, Akula SM. Cell Membrane-bound Kaposi's Sarcoma-associated Herpesvirus-encoded Glycoprotein B Promotes Virus Latency by Regulating Expression of Cellular Egr-1. Journal of Biological Chemistry. 2010;285(48):37491–502. doi: 10.1074/jbc.M110.159103 20864524

70. Reeves MB, Compton T. Inhibition of Inflammatory Interleukin-6 Activity via Extracellular Signal-Regulated Kinase–Mitogen-Activated Protein Kinase Signaling Antagonizes Human Cytomegalovirus Reactivation from Dendritic Cells. Journal of Virology. 2011;85(23):12750–8. doi: 10.1128/JVI.05878-11 21937636

71. Reeves MB, Breidenstein A, Compton T. Human cytomegalovirus activation of ERK and myeloid cell leukemia-1 protein correlates with survival of latently infected cells. Proceedings of the National Academy of Sciences. 2012;109(2):588–93. doi: 10.1073/pnas.1114966108 22203987

72. Kew V, Wills M, Reeves M. HCMV activation of ERK-MAPK drives a multi-factorial response promoting the survival of infected myeloid progenitors. J Mol Biochem. 2017;6(1):13–25. Epub 2017/05/12. 28491825; PubMed Central PMCID: PMC5421601.

73. Krishna BA, Poole EL, Jackson SE, Smit MJ, Wills MR, Sinclair JH. Latency-Associated Expression of Human Cytomegalovirus US28 Attenuates Cell Signaling Pathways To Maintain Latent Infection. mBio. 2017;8(6). doi: 10.1128/mBio.01754-17 29208743

74. Kew VG, Yuan J, Meier J, Reeves MB. Mitogen and Stress Activated Kinases Act Co-operatively with CREB during the Induction of Human Cytomegalovirus Immediate-Early Gene Expression from Latency. PLoS pathogens. 2014;10(6):e1004195. doi: 10.1371/journal.ppat.1004195 24945302

75. Crawford LB, Caposio P, Kreklywich C, Pham AH, Hancock MH, Jones TA, et al. Human Cytomegalovirus US28 Ligand Binding Activity Is Required for Latency in CD34+ Hematopoietic Progenitor Cells and Humanized NSG Mice. mBio. 2019;10(4). doi: 10.1128/mBio.01889-19 31431555

76. Ritchie MF, Yue C, Zhou Y, Houghton PJ, Soboloff J. Wilms Tumor Suppressor 1 (WT1) and Early Growth Response 1 (EGR1) Are Regulators of STIM1 Expression. Journal of Biological Chemistry. 2010;285(14):10591–6. doi: 10.1074/jbc.M109.083493 20123987

77. Bedadala GR, Pinnoji RC, Hsia S-CV. Early Growth Response gene 1 (Egr-1) regulates HSV-1 ICP4 and ICP22 gene expression. Cell Research. 2007;17:546. doi: 10.1038/cr.2007.44 17502875

78. Chang Y, Lee H-H, Chen Y-T, Lu J, Wu S-Y, Chen C-W, et al. Induction of the Early Growth Response 1 Gene by Epstein-Barr Virus Lytic Transactivator Zta. Journal of Virology. 2006;80(15):7748–55. doi: 10.1128/JVI.02608-05 16840354

79. Wu L-W. Role of Egr-1 in regulation of caveolin-1 gene expression in endothelial cells. Cancer Research. 2006;66(8 Supplement):31–.

80. Sinzger C, Hahn G, Digel M, Katona R, Sampaio KL, Messerle M, et al. Cloning and sequencing of a highly productive, endotheliotropic virus strain derived from human cytomegalovirus TB40/E. Journal of General Virology. 2008;89(2):359–68. doi: 10.1099/vir.0.83286–0

81. Warming S, Costantino N, Court DL, Jenkins NA, Copeland NG. Simple and highly efficient BAC recombineering using galK selection. Nucleic Acids Research. 2005;33(4):e36. doi: 10.1093/nar/gni035 15731329

82. Petrucelli A, Rak M, Grainger L, Goodrum F. Characterization of a novel Golgi apparatus-localized latency determinant encoded by human cytomegalovirus. J Virol. 2009;83(11):5615–29. Epub 2009/03/20. doi: 10.1128/JVI.01989-08 19297488; PubMed Central PMCID: PMC2681962.

83. Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic acids research. 2001;29(9):e45–e. doi: 10.1093/nar/29.9.e45 11328886.

84. Umashankar M, Rak M, Bughio F, Zagallo P, Caviness K, Goodrum F. Antagonistic Determinants Controlling Replicative and Latent States of Human Cytomegalovirus Infection. Journal of Virology. 2014. doi: 10.1128/jvi.03506-13 24623432

85. Hu Y, Smyth GK. ELDA: Extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays. Journal of Immunological Methods. 2009;347(1–2):70–8. doi: 10.1016/j.jim.2009.06.008 19567251

Štítky
Hygiena a epidemiologie Infekční lékařství Laboratoř

Článek vyšel v časopise

PLOS Pathogens


2019 Číslo 11
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#