#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Global Analysis of Mouse Polyomavirus Infection Reveals Dynamic Regulation of Viral and Host Gene Expression and Promiscuous Viral RNA Editing


Mouse polyomavirus (MPyV) is a small 5.3kb circular double-stranded DNA virus capable of causing tumors in a variety of tissues in immunocompromised mice. It has been a subject of study for over 60 years, yielding insights into a number of processes including tumorigenesis, cell cycle signaling, and transformation. This study serves to provide a global view of the MPyV infection by utilizing Illumina sequencing to observe changes in total RNA from both the virus and the host cell as well as applying new methods to more directly confirm the extent of A-to-I editing of viral RNA by host ADAR enzymes. This allows for a simultaneous observation of both host and viral transcriptional changes that occur as a result of early gene expression and the viral switch from early to late genes that occurs coincident with the initiation of DNA replication.


Vyšlo v časopise: Global Analysis of Mouse Polyomavirus Infection Reveals Dynamic Regulation of Viral and Host Gene Expression and Promiscuous Viral RNA Editing. PLoS Pathog 11(9): e32767. doi:10.1371/journal.ppat.1005166
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005166

Souhrn

Mouse polyomavirus (MPyV) is a small 5.3kb circular double-stranded DNA virus capable of causing tumors in a variety of tissues in immunocompromised mice. It has been a subject of study for over 60 years, yielding insights into a number of processes including tumorigenesis, cell cycle signaling, and transformation. This study serves to provide a global view of the MPyV infection by utilizing Illumina sequencing to observe changes in total RNA from both the virus and the host cell as well as applying new methods to more directly confirm the extent of A-to-I editing of viral RNA by host ADAR enzymes. This allows for a simultaneous observation of both host and viral transcriptional changes that occur as a result of early gene expression and the viral switch from early to late genes that occurs coincident with the initiation of DNA replication.


Zdroje

1. Hyde-DeRuyscher R, Carmichael GG. Polyomavirus early-late switch is not regulated at the level of transcription initiation and is associated with changes in RNA processing. Proc Natl Acad Sci USA. 1988;85:8993–7 2848251

2. Hyde-DeRuyscher R, Carmichael GG. Polyomavirus late pre-mRNA processing: DNA replication-associated changes in leader exon multiplicity suggest a role for leader-to-leader splicing in the early-late switch. J Virol. 1990;64(12):5823–32 2173769

3. Liu Z, Carmichael GG. Polyoma virus early-late switch: Regulation of late RNA accumulation by DNA replication. Proc Natl Acad Sci USA. 1993;90:8494–8 8397407

4. Liu Z., Batt D., Carmichael G.G. Targeted nuclear antisense RNA mimics natural antisense-induced degradation of polyoma virus early RNA. Proc Natl Acad Sci USA. 1994;91:4258–62 8183899

5. Beard P, Acheson NH, Maxwell IH. Strand-Specific Transcription of Polyoma Virus DNA Early in Productive Infection and in Transformed Cells. J Virol. 1976;17:20–6

6. Piper PW. Polyoma Virus Transcription Early During Productive Infection of Mouse 3T6 Cells. J Mol Biol. 1979;131:399–407 226720

7. Kamen R, Lindstrom DM, Shure H, Old RW. Virus-specific RNA in cells productively infected or transformed by polyoma virus. Cold Spring Harbor Symp Quant Biol. 1975;39:187–98 169059

8. Hunter T, Hutchinson M, Eckhart W. Translation of polyoma virus T antigens in vitro. Proc Natl Acad Sci USA. 1978;75:5917–21 216001

9. Tooze J. editor. Molecular Biology of Tumor Viruses: DNA Tumor Viruses. 2nd ed. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory; 1981

10. Benjamin TL. Polyoma Virus: Old Findings and New Challenges. Virology. 2001; 289:167–173 11689038

11. Treisman R, Kamen R. Structure of Polyoma Virus Late Nuclear RNA. J Mol Biol. 1981;148:273–301 6271970

12. Weil R, Kara J. Polyoma “tumor antigen”: an activator of chromosome replication? Proc Natl Acad Sci USA. 1970;67: 1011–7 4331714

13. Doherty J, Freund R. Polyomavirus large T antigen overcomes p53 dependent growth arrest. Oncogene. 1997;14: 1923–31 9150359

14. Weihua X, Ramanujam S, Lindner DJ, Kudaravalli RD, Freund R, Kalvakolanu DV. The polyoma virus T antigen interferes with interferon-inducible gene expression. Proc Natl Acad Sci USA. 1998;95:1085–90 9448289

15. Kautz AR, Weisshart K, Schneider A, Grosse F, Nasheuer H. Amino Acids 257 to 288 of Mouse p48 Control the Cooperation of Polyomavirus Large T Antigen, Replication Protein A, and DNA Polymerase alpha Primase To Synthesize DNA In Vitro. J Virol. 2001;75:8569–78 11507202

16. Xie A, Bermudez VP, Folk WR. Stimulation of DNA Replication from the Polyomavirus Origin by PCAF and GCN5 Acetyltransferases: Acetylation of Large T Antigen. Mol Cell Biol. 2002;22:7907–18 12391158

17. Yaniv M. Small DNA tumour viruses and their contributions to our understanding of transcription control. Virology. 2009;384:369–374 doi: 10.1016/j.virol.2008.11.002 19068262

18. Wang EH, Prives CP. DNA Helicase and Duplex DNA Fragment Unwinding Activities of Polyoma and Simian Virus 40 Large T Antigen Display Similarities and Differences. J Biol Chem. 1991;266:12668–75 1648101

19. Kern FG, Pellegrini S, Cowie A, Basilico C. Regulation of Polyomavirus Late Promoter Activity by Viral Early Proteins. J Virol. 1986;60:275–85 3018290

20. Rassoulzadegan M, Naghashfar Z, Cowie A, Carr A, Grisoni M, Kamen R, Cuzin F. Expression of the large T protein of polyoma virus promotes the establishment in culture of “normal” rodent fibroblast cell lines. Proc Natl Acad Sci USA. 1983;80:4354–8 6308618

21. Desjardins P, Pilon AA, Hassell JA, Mes-Masson A. Polyomavirus large T-antigen binds the ‘pRb related’ protein p130 through sequences in conserved region 2. Virus Res. 1997;47:85–90 9037740

22. Pilon AA, Desjardins P, Hassell JA, Mes-Masson A. Functional Implications of Mutations within Polyomavirus Large T Antigen Rb-Binding Domain: Effects on pRb and p107 Binding In Vitro and Immortalization Activity in Vivo. J Virol. 1996;70:4457–65 8676470

23. Cho S, Tian Y, Benjamin TL. Binding of p300/CBP Co-activators by Polyoma Large T Antigen. J Biol Chem. 2001;276:33533–9 11438528

24. Goodman RH, Smolik S. CBP/p300 in cell growth, transformation, and development. Genes Dev. 2000:14:1553–77 10887150

25. Brodsky JL, Pipas JM. Polyomavirus T Antigens: Molecular Chaperones for Multiprotein Complexes. J Virol. 1998;72:5329–34 9620985

26. Sheng Q, Love TM, Schaffhausen B. J Domain-Independent Regulation of the Rb Family by Polyomavirus Large T Antigen. J Virol. 2000;74:5280–90 10799605

27. Schaffhausen BS, Roberts TM. Lessons from polyoma middle T antigen on signaling and transformation: A DNA tumor virus contribution to the war on cancer. Virology. 2009;384:304–16 doi: 10.1016/j.virol.2008.09.042 19022468

28. Carmichael GG, Schaffhausen BS, Dorsky DI, Oliver DB, Benjamin TL. Carboxy terminus of polyoma middle-sized tumor antigen is required for attachment to membranes, associated protein kinase activities, and cell transformation. Proc Natl Acad Sci USA. 1982;79:3579–83 6179082

29. Pallas DC, Shahrik LK, Martin BL, Jaspers S, Miller TB, Brautigan DL, Roberts TM. Polyoma Small and Middle T Antigens and SV40 Small t Antigen Form Stable Complexes with Protein Phosphatase 2A. Cell. 1990;60:167–176 2153055

30. Walter G, Ruediger R, Slaughter C, Mumby M. Association of protein phosphatase 2A with polyoma virus medium tumor antigen. Proc Natl Acad Sci USA. 1990;87:2521–25 2157202

31. Courtneidge SA, Smith AE. Polyoma virus transforming protein associates with the product of the c-src cellular gene. Nature. 1983;303:435–39 6304524

32. Kornbluth S, Cheng SH, Markland W, Fukui Y, Hanafusa H. Association of p62c-yes with Polyomavirus Middle T-Antigen Mutants Correlates with Transforming Ability. J Virol. 1990;64:1584–9 1690822

33. Horak ID, Kawakami T, Gregory F, Robbins KC, Bolen JB. Association of p60fyn with Middle Tumor Antigen in Murine Polyomavirus-Transformed Rat Cells. J Virol. 1989;63:2343–7 2539523

34. Carmichael G, Schaffhausen BS, Mandel G, Liang TJ, Benjamin TL. Transformation by polyoma virus is drastically reduced by substitution of phenylalanine for tyrosine at residue 315 of middle-sized tumor antigen. Proc Natl Acad Sci USA. 1984;81:679–83 6322163

35. Harvey R, Oostra BA, Belsham GJ, Gillet P, Smith AE. An Antibody to a Synthetic Peptide Recognizes Polyomavirus Middle-T Antigen and Reveals Multiple In Vitro Tyrosine Phosphorylation Sites. Mol Cell Biol. 1984;4(7):1334–42 6095063

36. Hunter T, Hutchinson M, Eckhart W. Polyoma middle-sized T antigen can be phosphorylated on tyrosine at multiple sites in vitro. EMBO J. 1984;3: 73–9 6200324

37. Schaffhausen B, Benjamin TL. Comparison of Phosphorylation of Two Polyoma Virus Middle T Antigens In Vivo and In Vitro. J Virol. 1981;40:184–96 6169848

38. Campbell KS, Ogris E, Burke B, Su W, Auger KR, Druker BJ, Schaffhausen BS, Roberts TM, Pallas DC. Polyoma middle tumor antigen interacts with SHC protein via the NPTY (Asn-Pro-Thr-Tyr) motif in middle tumor antigen. Proc Natl Acad Sci USA. 1994;91:6344–8 8022784

39. Su W, Liu W, Schaffhausen BS, Roberts TM. Association of Polyomavirus Middle Tumor Antigen with Phospholipase C-gamma1. J Biol Chem. 1995;270:12331–4 7759472

40. Talmage DA, Freund R, Young AT, Dahl J, Dawe CJ, Benjamin TL. Phosphorylation of Middle T by pp60c-src: A Switch for Binding of Phosphatidylinositol 3-Kinase and Optimal Tumorigenesis. Cell. 1989;59:55–65 2551507

41. Andrabi S, Hwang JH, Choe JK, Roberts TM, Schaffhausen BS. Comparisons between Murine Polyomavirus and Simian Virus 40 Show Significant Differences in Small T Antigen Function. J Virol. 2011;85:10649–58 doi: 10.1128/JVI.05034-11 21835797

42. Schuchner S, Wintersberger E. Binding of Polyomavirus Small T Antigen to Protein Phosphatase 2A Is Required for Elimination of p27 and Support of S-Phase Induction in Concert with Large T Antigen. J Virol, 1999;73:9266–73 10516035

43. Rodriguez-Viciana P, Collins C, Fried M. Polyoma and SV40 proteins differentially regulate PP2A to activate distinct cellular signaling pathways involved in growth control. Proc Natl Acad Sci USA. 2006;103:19290–5 17158797

44. Qian W, Wiman KG. Polyoma Virus Middle T and Small t Antigens Cooperate to Antagonize p53-induced Cell Cycle Arrest and Apoptosis. Cell Growth Differ. 2000;11:31–9 10672901

45. Cahill KB, Roome AJ, Carmichael GG. Replication-Dependent Transactivation of the Polyomavirus Late Promoter. J Virol. 1990;6:992–1001

46. Gu R, Zhang Z, DeCerbo JN, Carmichael GG. Gene regulation by sense-antisense overlap of polyadenylation signals. RNA. 2009;15:1154–63 doi: 10.1261/rna.1608909 19390116

47. Acheson NH, Buetti E, Scherrer K, Weil R. Transcription of the Polyoma Virus Genome: Synthesis and Cleavage of Giant Late Polyoma-Specific RNA. Proc Natl Acad Sci USA. 1971;68:2231–5 4332250

48. Aloni Y, Locker H. Symmetrical in Vivo Transcription of Polyoma DNA and the Separation of Self-Complementary Viral and Cell RNA. Virology. 1973;54:495–505 4353523

49. Adami GR, Marlor CW, Barrett NL, Carmichael GG. Leader-to-Leader Splicing Is Required for Efficient Production and Accumulation of Polyomavirus Late mRNAs. J Virol. 1989;63:85–93 2535755

50. Heiser WC, Eckhart W. Polyoma Virus Early and Late mRNAs in Productively Infected Mouse 3T6 Cells. J Virol. 1982;44:175–188 6292484

51. Kumar M, Carmichael GG. Nuclear antisense RNA induces extensive adenosine modifications and nuclear retention of target transcripts. Proc Natl Acad Sci USA. 1997;94:3542–7 9108012

52. Bass BL. RNA Editing by Adenosine Deaminases that Act on RNA. Annu Rev Biochem. 2002;71:817–46 12045112

53. Turler H, Salomon C. Small and Middle T Antigens Contribute to Lytic and Abortive Polyomavirus Infection. J Virol. 1985;53:579–86 2578576

54. Kamen R, Shure H. Topography of Polyoma Virus Messenger RNA Molecules. Cell. 1976;7:361–71 181143

55. Acheson NH, Mieville F. Extent of Transcription of the E Strand of Polyoma Virus DNA During the Early Phase of Productive Infection. J Virol. 1978;28:885–94 215784

56. Turler H, Salomon C, Allet B, Weil R. Mapping of the three species of polyoma mRNA. Proc Natl Acad Sci USA, 1976;73: 1480–84 179087

57. Flavell AJ, Kamen R. Strand-Specific Transcription of Polyoma Virus DNA Late During Productive Infection. J Mol Biol. 1977;115:237–42 201760

58. Kamen R, Jat P, Treisman R, Favaloro J. 5’ Termini of Polyoma Virus Early Region Transcripts Synthesized in vivo by Wild-type Virus and Viable Deletion Mutants. J Mol Biol. 1982;159:189–224 6292432

59. Fenton RG, Basilico C. Changes in the topography of early region transcription during polyoma virus lytic infection. Proc Natl Acad Sci. 1982;79:7142–6 6296819

60. Ghosh PK, Lebowitz P. SImian Virus 40 early mRNA’s contain multiple 5’ termini upstream and downstream from a Hogness-Goldberg sequence; a shift in 5’ termini during the lytic cycle is mediated by large T antigen. J. Virol. 1981;40:224–40 6270376

61. Khalili K, Feigenbaum L, Khoury G. Evidence for a shift in 5’-termini of early viral RNA during the lytic cycle of JC Virus. Virology 1987;158:469–72 3035794

62. Riley MI, Yoo W, Mda N, Folk WR. Tiny T Antigen: an Autonomous Polyomavirus T Antigen Amino-Terminal Domain. J Virol, 1997;71:6068–74 9223500

63. Zhu S, Xiang J, Chen T, Chen L, Yang L. Prediction of constitutive A-to-I editing sites from human transcriptomes in the absence of genomic sequences. BMC Genomics, 2013;14:206 doi: 10.1186/1471-2164-14-206 23537002

64. Porath HT, Carmi S, Levanon EY. A genome-wide map of hyper-edited RNA reveals numerous new sites. Nat Commun. 2014;5:4726 doi: 10.1038/ncomms5726 25158696

65. van Holde K. E. (1988) Chromatin. Springer-Verlag, New York

66. Paschen SA, Rothbauer U, Kaldi K, Bauer MF, Neupert W, Brunner M. The role of the TIM8-13 complex in the import of Tim23 into mitochondria. EMBO J. 2000;19:6392–400 11101512

67. Chiu R, Angel P, Karin M. Jun-B Differs in Its Biological Properties from, and Is a Negative Regulator of, c-Jun. Cell. 1989;59:979–86 2513128

68. Schutte J, Viallet J, Nau M, Segal S, Fedorko J, Minna J. jun-B Inhibits and c-fos Stimulates the Transforming and Trans-Activating Activities of c-jun. Cell. 1989;59:987–97 2513129

69. Shaulian E, Karin M. AP-1 as a regulator of cell life and death. Nat Cell Biol. 2002;4:E131–6 11988758

70. Vuorio E, Crombrugghe B. The Family of Collagen Genes. Annu Rev Biochem. 1990:59:837–72 2197991

71. Ntambi M. Regulation of steroyl-CoA desaturase by polyunsaturated fatty acids and cholesterol. J Lipid Res. 1999;40:1549–58 10484602

72. Muir K, Hazim A, He Y, Peyressatre M, Kim DY, Song X, Beretta L. Proteomic and lipidomic signatures of lipid metabolism in NASH-associated hepatocellular carcinoma. Cancer Res. 2013;73:4722–31 doi: 10.1158/0008-5472.CAN-12-3797 23749645

73. Laux T, Fukami K, Thelen M, Golub T, Frey D, Caroni P. GAP43, MARCKS, and CAP23 modulate PI(4,5)P(2) at plasmalemmel rafts, and regulate cell cortex actin dynamics through a common mechanism. J Cell Biol. 2000;149:1455–72 10871285

74. Brooks G, Brooks SF, Goss MW. MARCKS functions as a novel growth suppressor in cells of melanocyte origin. Carcinogenesis. 1996;17:683–9 8625478

75. Bickerboller M, Tagscherer KE, Kloor M, Jansen L, Chang-Claude J, Brenner H, et al. Functional characterization of the tumor-suppressor MARCKS in colorectal cancer and its association with survival. Oncogene. 2015;34:1150–9 doi: 10.1038/onc.2014.40 24662837

76. Joseph CK, Qureshi SA, Wallace DJ, Foster DA. MARCKS protein is transcriptionally down-regulated in v-Src-transformed BALB/c 3T3 cells. J Biol Chem. 1992;267:1327–30 1370466

77. Tycowski KT, Shu MD, Steitz JA. Requirement for intron-encoded U22 small nucleolar RNA in 18S ribosomal RNA maturation. Science. 1994;266:1558–61 7985025

78. Ji P, Diedrichs S, Wang W, Boing S, Metzger R, Schneider PM, et al. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 2003;22:8031–41 12970751

79. Kielbasa SM, Klein H, Roider HG, Vingron M, Bluthgen N. TransFind-predicting transcriptional regulators for gene sets. Nucleic Acids Res, 2010;38:W275–80 doi: 10.1093/nar/gkq438 20511592

80. Bracken AP, Ciro M, Cocito A, Helin K. E2F target genes: unraveling the biology. TRENDS Biochem Sci, 2004;29:409–417 15362224

81. Aggarwal B. Nuclear factor-kB: The enemy within. Cancer Cell. 2004;6:203–208 15380510

82. Yoo W, Martin ME, Folk WR. PEA1 and PEA3 Enhancer Elements Are Primary Components of the Polyomavirus Late Transcription Initiator Element. J Virol. 1991;65:5391–5400 1654447

83. Sullivan CS, Grundhoff AT, Tevethia S, Pipas JT, Ganem D. SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells. Nature. 2005;435:682–6 15931223

84. Sullivan CS, Sung CK, Pack CD, Grundhoff A, Lukacher AE, Benjamin TL, Ganem D. Murine Polyomavirus encodes a microRNA that cleaves early RNA transcripts but is not essential for experimental infection. Virology. 2009;387:157–67 doi: 10.1016/j.virol.2009.02.017 19272626

85. Klucky B, Koch B, Radolf M,Steinlein P, Wintersberger E. Polyomavirus tumorantigens have a profound effect on gene expression in mouse fibroblasts. Oncogene 2004;23:4707–21 15122341

86. Artandi SE, DePinho R. Telomeres and telomerase in cancer. Carcinogenesis. 2010;31:9–18 doi: 10.1093/carcin/bgp268 19887512

87. Lai LB, Vioque A, Kirsebom LA, Gopalan V. Unexpected diversity of RNase P, an ancient tRNA processing enzyme: challenges and prospects. FEBS Lett. 2010;584:287–96 doi: 10.1016/j.febslet.2009.11.048 19931535

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2015 Číslo 9
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

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

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#