Dissecting HIVs Latent Menace 英文参考文献.docVIP

Synopsis DissectingHIV’sLatentMenace CaitlinSedwick* FreelanceScienceWriter,SanDiego,California,UnitedStatesofAmerica When HIV infects a T lymphocyte, it first inserts a copy of its genome into the cell’s DNA. This inserted virus, called a provirus,thenracestomakeasmanynew virusesaspossiblebeforeitshostcelldies. But in a few infected cells, HIV does not immediately turn its host into a viral factory. Instead, the provirus is carried around in the DNA of the cell as a of proteins, including those of the SWI/ SNFfamily. SWI/SNF is actually a complex of proteins assembled from several subunits. TherearetwomainvarietiesofSWI/SNF present in mammalian cells: one, called BAF, uniquely contains a subunit named BAF250, while the other, called PBAF, contains instead a different subunit. Ear- lier work conducted in Mahmoudi’s and others’ labs had produced conflicting results on how SWI/SNF proteins affect transcription of the HIV provirus—in somecases,SWI/SNFseemedtopromote viraltranscriptionandinotherstoinhibit it.Therefore,Rafatiandcolleaguesdecid- edtotakeacloserlookathowSWI/SNF affectsHIVtranscription. transcriptionally silent—or latent—pas- senger, only to explode back into action atalatertime,whenitshostcellattempts to participate in an immune response to infectionbyotherpathogens. BAF actively represses latent HIV by pushing/pulling the nuc1 nucleosome fromitsenergeticallypreferredlocation (DHS1) to a location that obscures the HIVtranscriptionalstartsite. BecausetheytargettheproductsofHIV transcription, current antiviral therapies like HAART can’t kill latent HIV. And because a full-blown infection can be re- establishedfromatinyreservoiroflatently infectedcells,virallatencyisanimportant contributortoourstruggleagainstHIV.In a paper published this month in PLoS Biology, Haleh Rafati, Tokameh Mah- moudi, and colleagues provide new in- sightsintohowHIVestablisheslatency. Because viruses frequently hijack cellu- lar processes for their own purposes, it is often i