Plos Pathogen：科学家们揭示蚊子中细菌阻断病毒传播的内在机制境决定！

 

沃尔巴克（氏）菌此前被认为能够降低蚊子传播病毒性疾病的能力，包括登革热、奇昆古尼亚热以及寨卡病毒等等。因此，科学家们希望了解能否通过给蚊子接种上述细菌起到降低疾病传播的效果。不过，此前其中的分子机制一直不清楚。

 

大部分关于沃尔巴克（氏）菌阻断病毒传播的研究都集中在蚊子对细菌的反应。然而，作者等人则研究了沃尔巴克（氏）菌直接对病毒的影响。他们通过一系列实验检测了在病毒感染细胞早期，细菌与病毒相互作用的详细过程。

 

DENVRNAisquicklydegradedinthepresenceofWolbachia.

 

(A)SchematicrepresentationoftheDENVgenomewithits5’&3’UTRsanddifferentDENVproteins.Thecolours(otherthanpaleblue)ofgenomicregionscorrespondtobarsingraphsinBandC.(BandC)Aag2andAag2-wMelcellswereinfectedwithDENV-2(MOI=10)andcollectedatdifferenttimepointsasshown.TotalcellularRNAwasusedtoanalyseRNAdegradationindifferentregionsoftheDENVgenome(colourcoded)from5’UTRto3’UTRthroughquantitativeRT-qPCRandnormalisedtoRPS-17RNAlevels.Dataareanalysedbycomparingthe5’UTRwith3’UTRandexpressedasmean±SEM(n=3).(D)RatioofgRNAnormalisedtoRPS-17RNAlevelsatdifferenttimepointsafterDENVinfection.(E)AnalysisofsubgenomicRNAinDENV-infectedAag2andAag2-wMelcells.DataareshownasrelativefoldchangeatdifferenttimepointsafterDENVinfection.

 

研究者们并没有发现沃尔巴克（氏）菌能够直接影响病毒早期的感染，然而，研究结果表明细菌能够阻止病毒入侵细胞后的复制过程。复制能力的降低伴随着病毒RNA的快速降解。此外，邮政局表明蚊子细胞中一种叫做XRN1的蛋白质或许在这一过程中起着十分关键的作用。

 

进一步的研究则表明沃尔巴克（氏）菌阻断病毒传播的能力依赖于病毒早期的剂量以及其复制的速度；复制速度较慢的病毒更容易被细菌阻断。

 

由于登革热是一类全球性的疾病，这一发现将有助于开发预防疾病发生与发展的新疗法。

 

Abstract

 

Wolbachiaiscurrentlybeingdevelopedasanoveltooltoblockthetransmissionofdengueviruses(DENV)byAedesaegypti.AnumberofmechanismshavebeenproposedtoexplaintheDENV-blockingphenotypeinmosquitoes,includingcompetitionforfattyacidslikecholesterol,manipulationofhostmiRNAsandupregulationofinnateimmunepathwaysinthemosquito.WeexaminedthevariousstagesintheDENVinfectionprocesstobetterunderstandthemechanismofWolbachia-mediatedvirusblocking(WMVB).OurresultssuggestthatinfectionwithWolbachiadoesnotinhibitDENVbindingorcellentry,butreducesvirusreplication.Incontrasttoapreviousreport,wealsoobservedasimilarreductioninreplicationofWestNilevirus(WNV).ThisreducedreplicationisassociatedwithrapidviralRNAdegradationinthecytoplasm.Wedidn’tfindaroleforhostmiRNAsinWMVB.Furtheranalysisshowedthatthe3’endofthevirussubgenomicRNAwasprotectedandaccumulatedovertimesuggestingthatthedegradationisXRN1-mediated.WealsofoundthatsubgenomicflavivirusRNAaccumulationinactivatedXRN1inmosquitocellsintheabsenceofWolbachiaandledtoenhancementofRNAdegradationinitspresence.DepletionofXRN1decreasedWMVBwhichwasassociatedwithasignificantincreaseinDENVRNA.WealsoobservedthatWMVBisinfluencedbyvirusMOIandrateofvirusreplication.AcomparativelyelevatedblockingwasobservedforslowlyreplicatingDENV,comparedtoWNV.SimilarresultswereobtainedwhileanalysingdifferentDENVserotypes.