Micro RNAs of Epstein-Barr Virus Promote Cell Cycle Progression and Prevent Apoptosis of Primary Human B Cells

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Cellular and viral microRNAs (miRNAs) are involved in many different processes of key importance and more than 10,000 miRNAs have been identified so far. In general, relatively little is known about their biological functions in mammalian cells because their phenotypic effects are often mild and many of their targets still await identification. The recent discovery that Epstein-Barr virus (EBV) and other herpesviruses produce their own, barely conserved sets of miRNAs suggests that these viruses usurp the host RNA silencing machinery to their advantage in contrast to the antiviral roles of RNA silencing in plants and insects. We have systematically introduced mutations in EBV's precursor miRNA transcripts to prevent their subsequent processing into mature viral miRNAs. Phenotypic analyses of these mutant derivatives of EBV revealed that the viral miRNAs of the BHRF1 locus inhibit apoptosis and favor cell cycle progression and proliferation during the early phase of infected human primary B cells. Our findings also indicate that EBV's miRNAs are not needed to control the exit from latency. The phenotypes of viral miRNAs uncovered by this genetic analysis indicate that they contribute to EBV-associated cellular transformation rather than regulate viral genes of EBV's lytic phase.

Vyšlo v časopise: Micro RNAs of Epstein-Barr Virus Promote Cell Cycle Progression and Prevent Apoptosis of Primary Human B Cells. PLoS Pathog 6(8): e32767. doi:10.1371/journal.ppat.1001063
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001063

Souhrn

Zdroje

1. KimVN

HanJ

SiomiMC

2009 Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 10 126 139

2. BartelDP

2004 MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116 281 297

3. LandgrafP

RusuM

SheridanR

SewerA

IovinoN

2007 A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129 1401 1414

4. BartelDP

2009 MicroRNAs: target recognition and regulatory functions. Cell 136 215 233

5. AmbrosV

2004 The functions of animal microRNAs. Nature 431 350 355

6. BushatiN

CohenSM

2007 microRNA functions. Annu Rev Cell Dev Biol 23 175 205

7. PfefferS

VoinnetO

2006 Viruses, microRNAs and cancer. Oncogene 25 6211 6219

8. VisoneR

CroceCM

2009 MiRNAs and cancer. Am J Pathol 174 1131 1138

9. GottweinE

CullenBR

2008 Viral and cellular microRNAs as determinants of viral pathogenesis and immunity. Cell Host Microbe 3 375 387

10. XiaoC

RajewskyK

2009 MicroRNA control in the immune system: basic principles. Cell 136 26 36

11. LewisBP

BurgeCB

BartelDP

2005 Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120 15 20

12. SelbachM

SchwanhausserB

ThierfelderN

FangZ

KhaninR

2008 Widespread changes in protein synthesis induced by microRNAs. Nature 455 58 63

13. RajewskyN

2006 microRNA target predictions in animals. Nat Genet 38 Suppl S8 13

14. WalzN

ChristallaT

TessmerU

GrundhoffA

2010 A global analysis of evolutionary conservation among known and predicted gammaherpesvirus microRNAs. J Virol 84 716 728

15. SchaferA

CaiX

BilelloJP

DesrosiersRC

CullenBR

2007 Cloning and analysis of microRNAs encoded by the primate gamma-herpesvirus rhesus monkey rhadinovirus. Virology 364 21 27

16. GrundhoffA

SullivanCS

GanemD

2006 A combined computational and microarray-based approach identifies novel microRNAs encoded by human gamma-herpesviruses. RNA 12 733 750

17. SamolsMA

SkalskyRL

MaldonadoAM

RivaA

LopezMC

2007 Identification of cellular genes targeted by KSHV-encoded microRNAs. PLoS Pathog 3 e65

18. ZiegelbauerJM

SullivanCS

GanemD

2009 Tandem array-based expression screens identify host mRNA targets of virus-encoded microRNAs. Nat Genet 41 130 134

19. KrutzfeldtJ

KuwajimaS

BraichR

RajeevKG

PenaJ

2007 Specificity, duplex degradation and subcellular localization of antagomirs. Nucleic Acids Res 35 2885 2892

20. KrutzfeldtJ

RajewskyN

BraichR

RajeevKG

TuschlT

2005 Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438 685 689

21. EbertMS

NeilsonJR

SharpPA

2007 MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 4 721 726

22. EisPS

TamW

SunL

ChadburnA

LiZ

2005 Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci U S A 102 3627 3632

23. van den BergA

KroesenBJ

KooistraK

de JongD

BriggsJ

2003 High expression of B-cell receptor inducible gene BIC in all subtypes of Hodgkin lymphoma. Genes Chromosomes Cancer 37 20 28

24. CostineanS

ZanesiN

PekarskyY

TiliE

VoliniaS

2006 Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice. Proc Natl Acad Sci U S A 103 7024 7029

25. GottweinE

MukherjeeN

SachseC

FrenzelC

MajorosWH

2007 A viral microRNA functions as an orthologue of cellular miR-155. Nature 450 1096 1099

26. SkalskyRL

SamolsMA

PlaisanceKB

BossIW

RivaA

2007 Kaposi's sarcoma-associated herpesvirus encodes an ortholog of miR-155. J Virol 81 12836 12845

27. DavidR

2010 miRNAs help KSHV lay low. Nature Reviews Microbiology 8 158 159

28. DelecluseHJ

HilsendegenT

PichD

ZeidlerR

HammerschmidtW

1998 Propagation and recovery of intact, infectious Epstein-Barr virus from prokaryotic to human cells. Proc Natl Acad Sci U S A 95 8245 8250

29. BaerR

BankierAT

BigginMD

DeiningerPL

FarrellPJ

1984 DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature 310 207 211

30. WarmingS

CostantinoN

CourtDL

JenkinsNA

CopelandNG

2005 Simple and highly efficient BAC recombineering using galK selection. Nucleic Acids Res 33 e36

31. AltmannM

HammerschmidtW

2005 Epstein-Barr virus provides a new paradigm: a requirement for the immediate inhibition of apoptosis. PLoS Biol 3 e404

32. NeuhierlB

FeederleR

HammerschmidtW

DelecluseHJ

2002 Glycoprotein gp110 of Epstein-Barr virus determines viral tropism and efficiency of infection. Proc Natl Acad Sci U S A 99 15036 15041

33. PrattZL

KuzembayevaM

SenguptaS

SugdenB

2009 The microRNAs of Epstein-Barr Virus are expressed at dramatically differing levels among cell lines. Virology 386 387 397

34. CullenBR

2009 Viral and cellular messenger RNA targets of viral microRNAs. Nature 457 421 425

35. BellareP

GanemD

2009 Regulation of KSHV lytic switch protein expression by a virus-encoded microRNA: an evolutionary adaptation that fine-tunes lytic reactivation. Cell Host Microbe 6 570 575

36. LeiX

BaiZ

YeF

XieJ

KimCG

2010 Regulation of NF-kappaB inhibitor IkappaBalpha and viral replication by a KSHV microRNA. Nat Cell Biol 12 193 199

37. LuF

StedmanW

YousefM

RenneR

LiebermanPM

2010 Epigenetic Regulation of Kaposi's Sarcoma-Associated Herpesvirus Latency by Virus-Encoded MicroRNAs That Target Rta and the Cellular Rbl2-DNMT Pathway. J Virol 84 2697 2706

38. UmbachJL

KramerMF

JurakI

KarnowskiHW

CoenDM

2008 MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs. Nature 454 780 783

39. MurphyE

VanicekJ

RobinsH

ShenkT

LevineAJ

2008 Suppression of immediate-early viral gene expression by herpesvirus-coded microRNAs: implications for latency. Proc Natl Acad Sci U S A 105 5453 5458

40. WenW

IwakiriD

YamamotoK

MaruoS

KandaT

2007 Epstein-Barr virus BZLF1 gene, a switch from latency to lytic infection, is expressed as an immediate-early gene after primary infection of B lymphocytes. J Virol 81 1037 1042

41. KallaM

SchmeinckA

BergbauerM

PichD

HammerschmidtW

2010 AP-1 homolog BZLF1 of Epstein-Barr virus has two essential functions dependent on the epigenetic state of the viral genome. Proc Natl Acad Sci U S A 107 850 855

42. KellyGL

LongHM

StylianouJ

ThomasWA

LeeseA

2009 An Epstein-Barr virus anti-apoptotic protein constitutively expressed in transformed cells and implicated in burkitt lymphomagenesis: the Wp/BHRF1 link. PLoS Pathog 5 e1000341

43. LoAK

ToKF

LoKW

LungRW

HuiJW

2007 Modulation of LMP1 protein expression by EBV-encoded microRNAs. Proc Natl Acad Sci U S A 104 16164 16169

44. LamN

SandbergML

SugdenB

2004 High physiological levels of LMP1 result in phosphorylation of eIF2 alpha in Epstein-Barr virus-infected cells. J Virol 78 1657 1664

45. LeeDY

SugdenB

2008 The LMP1 oncogene of EBV activates PERK and the unfolded protein response to drive its own synthesis. Blood 111 2280 2289

46. LeeDY

SugdenB

2008 The latent membrane protein 1 oncogene modifies B-cell physiology by regulating autophagy. Oncogene 27 2833 2842

47. CaiX

SchaferA

LuS

BilelloJP

DesrosiersRC

2006 Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS Pathog 2 e23

48. GrimsonA

FarhKK

JohnstonWK

Garrett-EngeleP

LimLP

2007 MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell 27 91 105

49. HammerschmidtW

SugdenB

1988 Identification and characterization of oriLyt, a lytic origin of DNA replication of Epstein-Barr virus. Cell 55 427 433

50. JanzA

OezelM

KurzederC

MautnerJ

PichD

2000 Infectious Epstein-Barr virus lacking major glycoprotein BLLF1 (gp350/220) demonstrates the existence of additional viral ligands. J Virol 74 10142 10152

51. FeederleR

KostM

BaumannM

JanzA

DrouetE

2000 The Epstein-Barr virus lytic program is controlled by the co-operative functions of two transactivators. EMBO J 19 3080 3089

52. Varkonyi-GasicE

WuR

WoodM

WaltonEF

HellensRP

2007 Protocol: a highly sensitive RT-PCR method for detection and quantification of microRNAs. Plant Methods 3 12