Hsp70 Isoforms Are Essential for the Formation of Kaposi’s Sarcoma-Associated Herpesvirus Replication and Transcription Compartments

Molecular chaperones from the HSP70 and HSP90 families have important roles in cell survival. Recent evidence has also implicated their functioning in a variety of diseases, including cancer. As such they have been identified as emerging drug targets. Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus which, like other herpesviruses, lytically replicates in virus-induced structures within the nucleus, termed replication and transcription compartments (RTCs). Here we developed a novel proteomic approach enhanced by subcellular fractionation to study the cellular protein composition of KSHV-induced RTCs. Results revealed that the constitutively expressed Hsc70 and the stress-inducible iHsp70 chaperones were significantly increased in the KSHV-induced RTCs. Importantly, inhibition of the ATPase function of these chaperones led to a marked reduction in KSHV RTCs formation and KSHV lytic replication. Notably, these results highlight the therapeutic potential of HSP70 inhibitors for the treatment of KSHV-related diseases, such as Kaposi’s sarcoma.

Vyšlo v časopise: Hsp70 Isoforms Are Essential for the Formation of Kaposi’s Sarcoma-Associated Herpesvirus Replication and Transcription Compartments. PLoS Pathog 11(11): e32767. doi:10.1371/journal.ppat.1005274
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1005274


Molecular chaperones from the HSP70 and HSP90 families have important roles in cell survival. Recent evidence has also implicated their functioning in a variety of diseases, including cancer. As such they have been identified as emerging drug targets. Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus which, like other herpesviruses, lytically replicates in virus-induced structures within the nucleus, termed replication and transcription compartments (RTCs). Here we developed a novel proteomic approach enhanced by subcellular fractionation to study the cellular protein composition of KSHV-induced RTCs. Results revealed that the constitutively expressed Hsc70 and the stress-inducible iHsp70 chaperones were significantly increased in the KSHV-induced RTCs. Importantly, inhibition of the ATPase function of these chaperones led to a marked reduction in KSHV RTCs formation and KSHV lytic replication. Notably, these results highlight the therapeutic potential of HSP70 inhibitors for the treatment of KSHV-related diseases, such as Kaposi’s sarcoma.


1. Saibil H. Chaperone machines for protein folding, unfolding and disaggregation. Nat Rev Mol Cell Bio. 2013;14(10):630–42.

2. Frydman J. Folding of newly translated proteins in vivo: The role of molecular chaperones. Annu Rev Biochem. 2001;70:603–47. 11395418

3. Macario AL, Conway de Macario E, Cappello F. Chaperones: General Characteristics and Classifications. The Chaperonopathies: Springer Netherlands; 2013. p. 15–33.

4. Sherman MY, Gabai VL. Hsp70 in cancer: back to the future. Oncogene. 2014. Epub 2014/10/28.

5. Whitesell L, Lindquist SL. HSP90 and the chaperoning of cancer. Nat Rev Cancer. 2005;5(10):761–72. 16175177

6. Witt SN. Hsp70 Molecular Chaperones and Parkinson's Disease. Biopolymers. 2010;93(3):218–28. doi: 10.1002/bip.21302 19768775

7. Geller R, Taguwa S, Frydman J. Broad action of Hsp90 as a host chaperone required for viral replication. Bba-Mol Cell Res. 2012;1823(3):698–706.

8. Mayer MP. Recruitment of Hsp70 chaperones: a crucial part of viral survival strategies. Reviews of Physiology Biochemistry and Pharmacology. 2005;153:1–46.

9. Gupta RS, Golding GB. Evolution of Hsp70 Gene and Its Implications Regarding Relationships between Archaebacteria, Eubacteria, and Eukaryotes. Journal of Molecular Evolution. 1993;37(6):573–82. 8114110

10. Lindquist S, Craig EA. The Heat Shock Proteins. Annu Rev Genet. 1988;22:631–77. 2853609

11. Gupta RS, Singh B. Phylogenetic Analysis of 70 Kd Heat Shock Protein Sequences Suggests a Chimeric Origin for the Eukaryotic Cell Nucleus. Curr Biol. 1994;4(12):1104–14. 7704574

12. Massey AJ. ATPases as Drug Targets: Insights from Heat Shock Proteins 70 and 90. Journal of Medicinal Chemistry. 2010;53(20):7280–6. doi: 10.1021/jm100342z 20608738

13. Powers MV, Jones K, Barillari C, Westwood I, van Montfort RLM, Workman P. Targeting HSP70 The second potentially druggable heat shock protein and molecular chaperone? Cell Cycle. 2010;9(8):1542–50. 20372081

14. Kim YS, Alarcon SV, Lee S, Lee MJ, Giaccone G, Neckers L, et al. Update on Hsp90 Inhibitors in Clinical Trial. Current Topics in Medicinal Chemistry. 2009;9(15):1479–92. 19860730

15. Jhaveri K, Taldone T, Modi S, Chiosis G. Advances in the clinical development of heat shock protein 90 (Hsp90) inhibitors in cancers. Bba-Mol Cell Res. 2012;1823(3):742–55.

16. Dhingra K, Valero V, Gutierrez L, Theriault R, Booser D, Holmes F, et al. Phase-II Study of Deoxyspergualin in Metastatic Breast Cancer. Invest New Drug. 1994;12(3):235–41.

17. Wischik CM, Bentham P, Wischik DJ, Seng KM. Tau aggregation inhibitor (TAI) therapy with rember arrests disease progression in mild and moderate Alzheimer's disease over 50 weeks. Alzheimer's & Dementia: The Journal of the Alzheimer's Association.4(4):T167.

18. Ganem D. KSHV and the pathogenesis of Kaposi sarcoma: listening to human biology and medicine. The Journal of Clinical Investigation. 2010;120(4):939–49. doi: 10.1172/JCI40567 20364091

19. Ganem D. KSHV infection and the pathogenesis of Kaposi's sarcoma. Annual Review of Pathology-Mechanisms of Disease. 2006;1(1):273–96.

20. Mesri EA, Cesarman E, Boshoff C. Kaposi's sarcoma and its associated herpesvirus. Nat Rev Cancer. 2010;10(10):707–19. doi: 10.1038/nrc2888 20865011

21. Wilson SJ, Tsao EH, Webb BLJ, Ye HT, Dalton-Griffin L, Tsantoulas C, et al. X box binding protein XBP-1s transactivates the Kaposi's sarcoma-associated herpesvirus (KSHV) ORF50 promoter, linking plasma cell differentiation to KSHV reactivation from latency. J Virol. 2007;81(24):13578–86. 17928342

22. Jackson BR, Noerenberg M, Whitehouse A. A Novel Mechanism Inducing Genome Instability in Kaposi's Sarcoma-Associated Herpesvirus Infected Cells. Plos Pathog. 2014;10(5).

23. Grundhoff A, Ganem D. Inefficient establishment of KSHV latency suggests an additional role for continued lytic replication in Kaposi sarcoma pathogenesis. J Clin Invest. 2004;113(1):124–36. 14702116

24. Goodwin DJ, Walters MS, Smith PG, Thurau M, Fickenscher H, Whitehouse A. Herpesvirus Saimiri open reading frame 50 (Rta) protein reactivates the lytic replication cycle in a persistently infected A549 cell line. J Virol. 2001;75(8):4008–13. 11264393

25. Lukac DM, Renne R, Kirshner JR, Ganem D. Reactivation of Kaposi's sarcoma-associated herpesvirus infection from latency by expression of the ORF 50 transactivator, a homolog of the EBV R protein. Virology. 1998;252(2):304–12. 9878608

26. Schmid M, Speiseder T, Dobner T, Gonzalez RA. DNA Virus Replication Compartments. J Virol. 2014;88(3):1404–20. doi: 10.1128/JVI.02046-13 24257611

27. McNamee EE, Taylor TJ, Knipe DM. A dominant-negative herpesvirus protein inhibits intranuclear targeting of viral proteins: Effects on DNA replication and late gene expression. J Virol. 2000;74(21):10122–31. 11024141

28. Monier K, Armas JCG, Etteldorf S, Ghazal P, Sullivan KF. Annexation of the interchromosomal space during viral infection. Nature Cell Biology. 2000;2(9):661–5. 10980708

29. Taylor TJ, McNamee EE, Day C, Knipe DM. Herpes simplex virus replication compartments can form by coalescence of smaller compartments. Virology. 2003;309(2):232–47. 12758171

30. Daikoku T, Kudoh A, Fujita M, Sugaya Y, Isomura H, Shirata N, et al. Architecture of replication compartments formed during Epstein-Barr virus lytic replication. J Virol. 2005;79(6):3409–18. 15731235

31. Wang Y, Li H, Tang Q, Maul GG, Yuan Y. Kaposi's sarcoma-associated herpesvirus ori-Lyt-dependent DNA replication: involvement of host cellular factors. J Virol. 2008;82(6):2867–82. Epub 2008/01/18. doi: 10.1128/JVI.01319-07 18199640

32. Taylor TJ, Knipe DM. Proteomics of herpes simplex virus replication compartments: Association of cellular DNA replication, repair, recombination, and chromatin remodeling proteins with ICP8. J Virol. 2004;78(11):5856–66. 15140983

33. Munday DC, Surtees R, Emmott E, Dove BK, Digard P, Barr JN, et al. Using SILAC and quantitative proteomics to investigate the interactions between viral and host proteomes. Proteomics. 2012;12(4–5):666–72. doi: 10.1002/pmic.201100488 22246955

34. Hiscox JA, Whitehouse A, Matthews DA. Nucleolar proteomics and viral infection. Proteomics. 2010;10(22):4077–86. doi: 10.1002/pmic.201000251 20661956

35. Korfali N, Fairley EL, Swanson S, Florens L, Schirmer E. Use of Sequential Chemical Extractions to Purify Nuclear Membrane Proteins for Proteomics Identification. In: Peirce M, Wait R, editors. Membrane Proteomics: Humana Press; 2009. p. 201–25.

36. Crisp M, Liu Q, Roux K, Rattner JB, Shanahan C, Burke B, et al. Coupling of the nucleus and cytoplasm: role of the LINC complex. J Cell Biol. 2006;172(1):41–53. 16380439

37. Starr DA, Han M. Role of ANC-1 in tethering nuclei to the actin cytoskeleton. Science. 2002;298(5592):406–9. 12169658

38. Mattout-Drubezki A, Gruenbaum Y. Dynamic interactions of nuclear lamina proteins with chromatin and transcriptional machinery. Cellular and Molecular Life Sciences. 2003;60(10):2053–63. 14618255

39. Stuurman N, Heins S, Aebi U. Nuclear lamins: Their structure, assembly, and interactions. Journal of Structural Biology. 1998;122(1–2):42–66. 9724605

40. Polioudaki H, Kourmouli N, Drosou V, Bakou A, Theodoropoulos PA, Singh PB, et al. Histones H3/H4 form a tight complex with the inner nuclear membrane protein LBR and heterochromatin protein 1. Embo Reports. 2001;2(10):920–5. 11571267

41. Chen WG, Sin SH, Wen KW, Damania B, Dittmer DP. Hsp90 Inhibitors Are Efficacious against Kaposi Sarcoma by Enhancing the Degradation of the Essential Viral Gene LANA, of the Viral Co-Receptor EphA2 as well as Other Client Proteins. Plos Pathog. 2012;8(11).

42. Vieira J, O'Hearn PM. Use of the red fluorescent protein as a marker of Kaposi's sarcoma-associated herpesvirus lytic gene expression. Virology. 2004;325(2):225–40. 15246263

43. Schumann S, Jackson BR, Baquero-Perez B, Whitehouse A. Kaposi's Sarcoma-Associated Herpesvirus ORF57 Protein: Exploiting All Stages of Viral mRNA Processing. Viruses-Basel. 2013;5(8):1901–23.

44. Hughes DJ, Wood JJ, Jackson BR, Baquero-Perez B, Whitehouse A. NEDDylation Is Essential for Kaposi's Sarcoma- Associated Herpesvirus Latency and Lytic Reactivation and Represents a Novel Anti-KSHV Target. Plos Pathog. 2015;11(3).

45. Du GX, Stinski MF. Interaction Network of Proteins Associated with Human Cytomegalovirus IE2-p86 Protein during Infection: A Proteomic Analysis. Plos One. 2013;8(12).

46. Benson JD, Huang ES. Human cytomegalovirus induces expression of cellular topoisomerase II. J Virol. 1990;64(1):9–15. Epub 1990/01/01. 2152837

47. Advani SJ, Weichselbaum RR, Roizman B. Herpes simplex virus 1 activates cdc2 to recruit topoisomerase II alpha for post-DNA synthesis expression of late genes. P Natl Acad Sci USA. 2003;100(8):4825–30.

48. Nakamura H, Lu M, Gwack Y, Souvlis J, Zeichner SL, Jung JU. Global changes in Kaposi's sarcoma-associated virus gene expression patterns following expression of a tetracycline-inducible Rta transactivator. J Virol. 2003;77(7):4205–20. 12634378

49. Okeefe RT, Henderson SC, Spector DL. Dynamic Organization of DNA Replication in Mammalian Cell Nuclei: Spatially and Temporally Defined Replication of Chromosome-Specific Alpha-Satellite DNA Sequences. J Cell Biol. 1992;116(5):1095–110. 1740468

50. Seiler JA, Conti C, Syed A, Aladjem MI, Pommier Y. The intra-S-phase checkpoint affects both DNA replication initiation and elongation: Single-cell and -DNA fiber analyses. Mol Cell Biol. 2007;27(16):5806–18. 17515603

51. Munro S, Pelham HRB. A C-Terminal Signal Prevents Secretion of Luminal ER Proteins. Cell. 1987;48(5):899–907. 3545499

52. Schlecht R, Scholz SR, Dahmen H, Wegener A, Sirrenberg C, Musil D, et al. Functional Analysis of Hsp70 Inhibitors. Plos One. 2013;8(11).

53. Macias AT, Williamson DS, Allen N, Borgognoni J, Clay A, Daniels Z, et al. Adenosine-Derived Inhibitors of 78 kDa Glucose Regulated Protein (Grp78) ATPase: Insights into Isoform Selectivity. Journal of Medicinal Chemistry. 2011;54(12):4034–41. doi: 10.1021/jm101625x 21526763

54. Massey AJ, Williamson DS, Browne H, Murray JB, Dokurno P, Shaw T, et al. A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells. Cancer Chemotherapy and Pharmacology. 2009;66(3):535–45. doi: 10.1007/s00280-009-1194-3 20012863

55. Rodriguez A, Perez-Gonzalez A, Nieto A. Influenza virus infection causes specific degradation of the largest subunit of cellular RNA polymerase II. J Virol. 2007;81(10):5315–24. 17344288

56. Clarke PA, Hostein I, Banerji U, Di Stefano F, Maloney A, Walton M, et al. Gene expression profiling of human colon cancer cells following inhibition of signal transduction by 17-allylamino-17-demethoxygeldanamycin, an inhibitor of hsp90 molecular chaperone. Oncogene. 2000;19(36):4125–33. 10962573

57. Banerji U, O'Donnell A, Scurr M, Pacey S, Stapleton S, Asad Y, et al. Phase I Pharmacokinetic and Pharmacodynamic Study of 17-Allylamino, 17-Demethoxygeldanamycin in Patients With Advanced Malignancies. Journal of Clinical Oncology. 2005;23(18):4152–61. 15961763

58. Burch AD, Weller SK. Herpes simplex virus type 1 DNA polymerase requires the mammalian chaperone Hsp90 for proper localization to the nucleus. J Virol. 2005;79(16):10740–9. 16051866

59. Chase G, Deng T, Fodor E, Leung BW, Mayer D, Schwemmle M, et al. Hsp90 inhibitors reduce influenza virus replication in cell culture. Virology. 2008;377(2):431–9. doi: 10.1016/j.virol.2008.04.040 18570972

60. Geller R, Vignuzzi M, Andino R, Frydman J. Evolutionary constraints on chaperone-mediated folding provide an antiviral approach refractory to development of drug resistance. Genes & Development. 2007;21(2):195–205.

61. Geller R, Andino R, Frydman J. Hsp90 Inhibitors Exhibit Resistance-Free Antiviral Activity against Respiratory Syncytial Virus. Plos One. 2013;8(2).

62. Connor JH, McKenzie MO, Parks GD, Lyles DS. Antiviral activity and RNA polymerase degradation following Hsp90 inhibition in a range of negative strand viruses. Virology. 2007;362(1):109–19. Epub 2007/01/30. 17258257

63. Niles AL, Moravec RA, Riss TL. Update on in vitro cytotoxicity assays for drug development. Expert Opinion on Drug Discovery. 2008;3(6):655–69. doi: 10.1517/17460441.3.6.655 23506147

64. Wen W, Liu WX, Shao YF, Chen L. VER-155008, a small molecule inhibitor of HSP70 with potent anti-cancer activity on lung cancer cell lines. Experimental Biology and Medicine. 2014;239(5):638–45. doi: 10.1177/1535370214527899 24676905

65. Thulasiraman V, Yang CF, Frydman J. In vivo newly translated polypeptides are sequestered in a protected folding environment. Embo J. 1999;18(1):85–95. 9878053

66. Deng HY, Young A, Sun R. Auto-activation of the rta gene of human herpesvirus-8 Kaposi's sarcoma-associated herpesvirus. J Gen Virol. 2000;81:3043–8. 11086135

67. Song MJ, Brown HJ, Wu TT, Sun R. Transcription activation of polyadenylated nuclear RNA by Rta in human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus. J Virol. 2001;75(7):3129–40. 11238840

68. Bu W, Palmeri D, Krishnan R, Marin R, Aris VM, Soteropoulos P, et al. Identification of Direct Transcriptional Targets of the Kaposi's Sarcoma-Associated Herpesvirus Rta Lytic Switch Protein by Conditional Nuclear Localization. J Virol. 2008;82(21):10709–23. doi: 10.1128/JVI.01012-08 18715905

69. Song MJ, Deng HY, Sun R. Comparative study of regulation of RTA-responsive genes in Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8. J Virol. 2003;77(17):9451–62. 12915560

70. Ellison TJ, Izumiya Y, Izumiya C, Luciw PA, Kung HJ. A comprehensive analysis of recruitment and transactivation potential of K-Rta and K-bZIP during reactivation of Kaposi's sarcoma-associated herpesvirus. Virology. 2009;387(1):76–88. doi: 10.1016/j.virol.2009.02.016 19269659

71. Conrad NK, Steitz JA. A Kaposi's sarcoma virus RNA element that increases the nuclear abundance of intronless transcripts. Embo J. 2005;24(10):1831–41. 15861127

72. Massimelli MJ, Kang JG, Majerciak V, Le SY, Liewehr DJ, Steinberg SM, et al. Stability of a Long Noncoding Viral RNA Depends on a 9-nt Core Element at the RNA 5 ' End to Interact with Viral ORF57 and Cellular PABPC1. Int J Biol Sci. 2011;7(8):1145–60. 22043172

73. Wu FY, Wang SE, Tang Q-Q, Fujimuro M, Chiou C-J, Zheng Q, et al. Cell Cycle Arrest by Kaposi's Sarcoma-Associated Herpesvirus Replication-Associated Protein Is Mediated at both the Transcriptional and Posttranslational Levels by Binding to CCAAT/Enhancer-Binding Protein α and p21(CIP-1). J Virol. 2003;77(16):8893–914. 12885907

74. Borah S, Darricarrere N, Darnell A, Myoung J, Steitz JA. A Viral Nuclear Noncoding RNA Binds Re-localized Poly(A) Binding Protein and Is Required for Late KSHV Gene Expression. Plos Pathog. 2011;7(10).

75. Burch AD, Weller SK. Nuclear sequestration of cellular chaperone and proteasomal machinery during herpes simplex virus type 1 infection. J Virol. 2004;78(13):7175–85. 15194794

76. Li L, Johnson LA, Dai-Ju JQ, Sandri-Goldin RM. Hsc70 Focus Formation at the Periphery of HSV-1 Transcription Sites Requires ICP27. Plos One. 2008;3(1).

77. Livingston CM, Ifrim MF, Cowan AE, Weller SK. Virus-Induced Chaperone-Enriched (VICE) Domains Function as Nuclear Protein Quality Control Centers during HSV-1 Infection. Plos Pathog. 2009;5(10).

78. Wickner S, Hoskins J, Mckenney K. Function of Dnaj and Dnak as Chaperones in Origin-Specific DNA-Binding by Repa. Nature. 1991;350(6314):165–7. 2005967

79. Wickner SH. Three Escherichia coli heat shock proteins are required for P1 plasmid DNA replication: formation of an active complex between E. coli DnaJ protein and the P1 initiator protein. Proceedings of the National Academy of Sciences. 1990;87(7):2690–4.

80. Giraldo R, Diaz-Orejas R. Similarities between the DNA replication initiators of Gram-negative bacteria plasmids (RepA) and eukaryotes (Orc4p)/archaea (Cdc6p). P Natl Acad Sci USA. 2001;98(9):4938–43.

81. Liu JS, Kuo SR, Makhov AM, Cyr DM, Griffith JD, Broker TR, et al. Human Hsp70 and Hsp40 chaperone proteins facilitate human papillomavirus-11 E1 protein binding to the origin and stimulate cell-free DNA replication. J Biol Chem. 1998;273(46):30704–12. 9804845

82. Lin BY, Makhov AM, Griffith JD, Broker TR, Chow LT. Chaperone proteins abrogate inhibition of the human papillomavirus (HPV) E1 replicative helicase by the HPV E2 protein. Mol Cell Biol. 2002;22(18):6592–604. 12192057

83. Le Gac NT, Boehmer PE. Activation of the herpes simplex virus type-1 origin-binding protein (UL9) by heat shock proteins. J Biol Chem. 2002;277(7):5660–6. 11711536

84. Alfano C, Mcmacken R. Heat Shock Protein-Mediated Disassembly of Nucleoprotein Structures Is Required for the Initiation of Bacteriophage Lambda DNA Replication. J Biol Chem. 1989;264(18):10709–18. 2543679

85. Alfano C, Mcmacken R. Ordered Assembly of Nucleoprotein Structures at the Bacteriophage Lambda Replication Origin during the Initiation of DNA Replication. J Biol Chem. 1989;264(18):10699–708. 2525129

86. Bechtel JT, Winant RC, Ganem D. Host and viral proteins in the virion of Kaposi's sarcoma-associated herpesvirus. J Virol. 2005;79(8):4952–64. 15795281

87. Zhu FX, Chong JM, Wu L, Yuan Y. Virion proteins of Kaposi's sarcoma-associated herpesvirus. J Virol. 2005;79(2):800–11. Epub 2004/12/23. 15613308

88. Murphy ME. The HSP70 family and cancer. Carcinogenesis. 2013;34(6):1181–8. doi: 10.1093/carcin/bgt111 23563090

89. Rerole AL, Gobbo J, De Thonel A, Schmitt E, de Barros JPP, Hammann A, et al. Peptides and Aptamers Targeting HSP70: A Novel Approach for Anticancer Chemotherapy. Cancer Research. 2011;71(2):484–95. doi: 10.1158/0008-5472.CAN-10-1443 21224349

90. Miyata Y, Rauch JN, Jinwal UK, Thompson AD, Srinivasan S, Dickey CA, et al. Cysteine Reactivity Distinguishes Redox Sensing by the Heat-Inducible and Constitutive Forms of Heat Shock Protein 70. Chem Biol. 2012;19(11):1391–9. doi: 10.1016/j.chembiol.2012.07.026 23177194

91. Kamal A, Thao L, Sensintaffar J, Zhang L, Boehm MF, Fritz LC, et al. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature. 2003;425(6956):407–10. 14508491

92. Wen KW, Damania B. Hsp90 and Hsp40/Erdj3 are required for the expression and anti-apoptotic function of KSHV K1. Oncogene. 2010;29(24):3532–44. doi: 10.1038/onc.2010.124 20418907

93. Dai-Ju JQ, Li L, Johnson LA, Sandri-Goldin RM. ICP27 interacts with the C-terminal domain of RNA polymerase II and facilitates its recruitment to herpes simplex virus 1 transcription sites, where it undergoes proteasomal degradation during infection. J Virol. 2006;80(7):3567–81. Epub 2006/03/16. 16537625

94. Varnum SM, Streblow DN, Monroe ME, Smith P, Auberry KJ, Pasa-Tolic L, et al. Identification of proteins in human cytomegalovirus (HCMV) particles: the HCMV proteome (vol 78, pg 10960, 2004). J Virol. 2004;78(23):13395–.

95. Johannsen E, Luftig M, Chase MR, Weicksel S, Cahir-McFarland E, Illanes D, et al. Proteins of purified Epstein-Barr virus. P Natl Acad Sci USA. 2004;101(46):16286–91.

96. Loret S, Guay G, Lippe R. Comprehensive characterization of extracellular herpes simplex virus type 1 virions. J Virol. 2008;82(17):8605–18. doi: 10.1128/JVI.00904-08 18596102

97. Stegen C, Yakova Y, Henaff D, Nadjar J, Duron J, Lippe R. Analysis of Virion-Incorporated Host Proteins Required for Herpes Simplex Virus Type 1 Infection through a RNA Interference Screen. Plos One. 2013;8(1).

98. Jackson BR, Boyne JR, Noerenberg M, Taylor A, Hautbergue GM, Walsh MJ, et al. An Interaction between KSHV ORF57 and UIF Provides mRNA-Adaptor Redundancy in Herpesvirus Intronless mRNA Export. Plos Pathog. 2011;7(7).

99. Whitehouse A, Stevenson AJ, Cooper M, Meredith DM. Identification of a cis-acting element within the herpesvirus saimiri ORF 6 promoter that is responsive to the HVS.R transactivator. J Gen Virol. 1997;78(6):1411–5.

100. Harrison SM, Whitehouse A. Kaposi’s sarcoma-associated herpesvirus (KSHV) Rta and cellular HMGB1 proteins synergistically transactivate the KSHV ORF50 promoter. FEBS Letters. 2008;582(20):3080–4. doi: 10.1016/j.febslet.2008.07.055 18692049

101. Knight LM, Stakaityte G, Wood JJ, Abdul-Sada H, Griffiths DA, Howell GJ, et al. Merkel Cell Polyomavirus Small T Antigen Mediates Microtubule Destabilization To Promote Cell Motility and Migration. J Virol. 2015;89(1):35–47. doi: 10.1128/JVI.02317-14 25320307

102. Hall KT, Stevenson AJ, Goodwin DJ, Gibson PC, Markham AF, Whitehouse A. The activation domain of herpesvirus saimiri R protein interacts with the TATA-binding protein. J Virol. 1999;73(12):9756–63. 10559285

103. Emmott E, Munday D, Bickerton E, Britton P, Rodgers MA, Whitehouse A, et al. The Cellular Interactome of the Coronavirus Infectious Bronchitis Virus Nucleocapsid Protein and Functional Implications for Virus Biology. J Virol. 2013;87(17):9486–500. doi: 10.1128/JVI.00321-13 23637410

104. Goodwin DJ, Hall KT, Giles MS, Calderwood MA, Markham AF, Whitehouse A. The carboxy terminus of the herpesvirus saimiri ORF 57 gene contains domains that are required for transactivation and transrepression. J Gen Virol. 2000;81:2253–65. 10950983

105. Goodwin DJ, Whitehouse A. A γ-2 Herpesvirus Nucleocytoplasmic Shuttle Protein Interacts with Importin α1 and α5. J Biol Chem. 2001;276(23):19905–12. 11278515

106. Boyne JR, Whitehouse A. Nucleolar disruption impairs Kaposi’s sarcoma-associated herpesvirus ORF57-mediated nuclear export of intronless viral mRNAs. FEBS Letters. 2009;583(22):3549–56. doi: 10.1016/j.febslet.2009.10.040 19850040

107. Griffiths DA, Abdul-Sada H, Knight LM, Jackson BR, Richards K, Prescott EL, et al. Merkel Cell Polyomavirus Small T Antigen Targets the NEMO Adaptor Protein To Disrupt Inflammatory Signaling. J Virol. 2013;87(24):13853–67. doi: 10.1128/JVI.02159-13 24109239

Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens

2015 Číslo 11
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle

Zvýšte si kvalifikáciu online z pohodlia domova

Eozinofilní granulomatóza s polyangiitidou
nový kurz

Betablokátory a Ca antagonisté z jiného úhlu
Autori: prof. MUDr. Michal Vrablík, Ph.D., MUDr. Petr Janský

Autori: doc. MUDr. Petr Čáp, Ph.D.

Farmakoterapie akutní a chronické bolesti

Získaná hemofilie - Povědomí o nemoci a její diagnostika

Všetky kurzy
Zabudnuté heslo

Nemáte účet?  Registrujte sa

Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.


Nemáte účet?  Registrujte sa