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rev bras hematol hemoter. 2015;37(6):357–358

w w w . r b h h . o r g

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Scientific

Comment

Torque

teno

virus:

a

ubiquitous

virus

Karen

Brajão

de

Oliveira

UniversidadeEstadualdeLondrina(UEL),Londrina,PR,Brazil

Torquetenovirus(TTV)isanon-envelopedhumanDNAvirus isolatedbyNishizawaetal.in1997.1TTV,recentlyclassified

astheAlphatorquevirusgenuswithintheAnelloviridaefamilyby theInternationalCommitteeonTaxonomyofViruses(ICTV), wasthefirsthumanviruswithasingle-strandedcircularDNA genometobeidentified.2Thusfar,fivemaingeneticgroups

(Groups1–5)involvingatleast39genotypeshavebeen identi-fiedbasedonphylogeneticanalysis.3

The TTV genome can be divided into an untranslated region(UTR)of1.2kbandapotentialcodingregionof2.6kb. The UTR is relatively conserved, suggesting that it plays an importantregulatory role in viral replication. The cod-ingregioncontainstwolargeopenreadingframes:ORF1and ORF2.Severalotheropenreadingframeshavebeendescribed, andthepeptidesthattheyencodedifferinlengthfordifferent isolates.4

Thisvirus is characterizedbyanextremely high preva-lence,withrelativelyuniformdistributionworldwideand a high level of genomic heterogeneity.4 Although this virus

hasaveryhighprevalenceinthegeneralpopulationacross theglobe,neitheritsinteractionwithitshostsnoritsdirect involvementintheetiologyofspecificdiseasesisfully under-stood.

After the discovery of TTV, its detection has been by polymerasechainreaction(PCR) withprimerstargetingthe ORF1(N22region,thefirstdescribedsequence),nevertheless primersderivedfromtheN22regioncandetectonlyaportion of TTV variants mainly representing genetic group 1 TTV (Genotypes1–6).5,6AstheUTRsoftheviralgenomearemore

conservedwhencomparedtotheORFregions,UTR-targeting primers(usedlaterforthedetectionofTTVDNA)candetect

DOIoforiginalarticle:http://dx.doi.org/10.1016/j.bjhh.2015.07.005.

SeepaperbyMazzolaetal.inRevBrasHematolHemoter.2015;37(5):336–40.

Correspondingauthorat:DepartamentodeCiênciasPatológicas,UniversidadeEstadualdeLondrina,CampusUniversitário,86051-970

Londrina,PR,Brazil.

E-mailaddress:karen.brajao@gmail.com

essentiallyallknownTTVstrainsreported,therebydetectinga largernumberofgenotypesgivingahigherdetectionrate.5,7,8

In this issue of the Revista Brasileira de Hematologiae Hemoterapia, there is an important study entitled “Preva-lenceofTorquetenovirusinhealthydonorsofParanáState, southernBrazil”.Inthisarticle,theauthorsdemonstratedthe prevalenceoftheTTVinhealthydonorsinthenorthernand northwesternregionsofthestateofParaná,southernBrazil, bynestedPCRusingasetofprimersfortheN22region.9

TheauthorsdemonstratedahighprevalenceofTTV(69%) amonghealthyblooddonorsbyusingprimerstargetingthe N22region.Itisthereforepossiblethatiftheauthorshadused primersforthe UTRstheprevalencewould havebeeneven higher.

Thishigh prevalenceofthe virusmakesitalmost ubiq-uitousinthehumanpopulationandabletoevadeclearance by the host immune response thereby establishing long-termpersistentinfections.10Inthiscontextwecanhighlight

theMicroRNAs(miRNAs), small22ntnoncodingRNAsthat direct posttranscriptional gene regulation, that have been recognized as important regulators of gene expression in many eukaryotes and even in viruses.11 Emerging themes

ofviral miRNAfunctionincludeimmune evasion, prolong-ing longevity of host cells, and regulation of persistent infection.12–14

The TTV makes use of viral miRNAs to modulate the innateimmuneresponseand promoteits persistence. Kin-caidetal.15showedthattheTTVencodesamiRNAinvivothat

targetsN-myc(andSTAT)interactor(NMI),thusmediatinga decreasedresponsetointerferonsandincreasedcellular pro-liferationinthepresenceofinterferon.Thesefactssupportthe

http://dx.doi.org/10.1016/j.bjhh.2015.07.009

(2)

358

revbrashematolhemoter.2015;37(6):357–358

theorythatmiRNA-mediatedimmuneevasioncontributesto theimmenseubiquityofthesevirusesbyantagonizingthe hostantiviralresponse.

IthasbeensuggestedthatTTVinfectionisassociatedwith manydiseases,howeverthereisnodirectevidenceoflinks betweeninfection and specific clinical diseases,and many questionsremaintobeclarifiedforexample,howcanTTV interfereinmanypathologicalprocessesandinthe dysregu-lationoftheimmunesystem?Thesequestionsundoubtedly representrichfieldsforresearchonTTV.

Conflicts

of

interest

Theauthordeclaresnoconflictsofinterest.

r

e

f

e

r

e

n

c

e

s

1. NishizawaT,OkamotoH,KonishiK,YoshizawaH,Miyakawa

Y,MayumiM.AnovelDNAvirus(TTV)associatedwith

elevatedtransaminaselevelsinposttransfusionhepatitisof

unknownetiology.BiochemBiophysResCommun.

1997;241(1):92–7.

2. KingAMQ,AdamsMJ,LefkowitzEJ.Virustaxonomy:ninth

reportoftheinternationalcommitteeontaxonomyof

viruses.Amsterdam:Elsevier;2011.p.331–41.

3. MiZ,YuanX,PeiG,WangW,AnX,ZhangZ,etal.

High-throughputsequencingexclusivelyidentifiedanovel

Torquetenovirusgenotypeinserumofapatientwithfatal

fever.VirolSin.2014;29(2):112–8.

4. SpandoleS,CimponeriuD,BercaLM,Mih ˘aescuG.Human

anelloviruses:anupdateofmolecular,epidemiologicaland

clinicalaspects.ArchVirol.2015;160(4):893–908.

5.PengYH,NishizawaT,TakahashiM,IshikawaT,YoshikawaA,

OkamotoH.AnalysisoftheentiregenomesofthirteenTT

virusvariantsclassifiableintothefourthandfifthgenetic

groups,isolatedfromviremicinfants.ArchVirol.

2002;147(1):21–41.

6.HussainT,ManzoorS,WaheedY,TariqH,HanifK.

PhylogeneticanalysisofTorqueTenoVirusgenomefrom

Pakistaniisolateandincidenceofco-infectionamong

HBV/HCVinfectedpatients.VirolJ.2012;9:320.

7.TakahashiK,HoshinoH,OhtaY,YoshidaN,MishiroS.Very

highprevalenceofTTvirus(TTV)infectioningeneral

populationofJapanrevealedbyanewsetofPCRprimers.

HepatolRes.1998;12(3):233–9.

8.HinoS.TTV,anewhumanviruswithsinglestrandedcircular

DNAgenome.RevMedVirol.2002;12(3):151–8.

9.MazzolaJC,SaitoPK,YamakawaRH,WatanabeMA,daSilva

JuniorWV,MattaAC,etal.Prevalenceoftorquetenovirusin

healthydonorsofParanáState,southernBrazil.RevBras

HematolHemoter.2015;37(5):336–40.

10.OkamotoH.HistoryofdiscoveriesandpathogenicityofTT

viruses.In:deVilliersE-M,zurHausenH,editors.TTviruses.

Currenttopicsinmicrobiologyandimmunology,vol.331.

Berlin:Springer;2009.p.1–20.

11.CullenBR.VirusesandmicroRNAs.NatGenet.2006;38

Suppl.:S25–30.

12.BossIW,RenneR.ViralmiRNAs:toolsforimmuneevasion.

CurrOpinMicrobiol.2010;13(4):540–5.

13.KincaidRP,SullivanCS.Virus-encodedmicroRNAs:an

overviewandalooktothefuture.PLoSPathog.

2012;8(12):e1003018.

14.CullenBR.MicroRNAsasmediatorsofviralevasionofthe

immunesystem.NatImmunol.2013;14(3):205–10.

15.KincaidRP,BurkeJM,CoxJC,deVilliersEM,SullivanCS.A

humantorquetenovirusencodesamicroRNAthatinhibits

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