Fidelity of Target Site Duplication and Sequence Preference during Integration of Xenotropic Murine Leukemia Virus-Related Virus 英文参考文献.docVIP

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Fidelity of Target Site Duplication and Sequence Preference during Integration of Xenotropic Murine Leukemia Virus-Related Virus 英文参考文献.doc

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Fidelity of Target Site Duplication and Sequence Preference during Integration of Xenotropic Murine Leukemia Virus-Related Virus 英文参考文献

FidelityofTargetSiteDuplicationandSequence PreferenceduringIntegrationofXenotropicMurine LeukemiaVirus-RelatedVirus SangguKim1,AliceRusmevichientong2,BeihuaDong3,RolandRemenyi2,RobertH.Silverman3, SamsonA.Chow1,2 * 1BiomedicalEngineeringInterdepartmentalProgram,UniversityofCaliforniaLosAngeles,LosAngeles,California,UnitedStatesofAmerica,2DepartmentofMolecular andMedicalPharmacology,MolecularBiologyInstitute,andUniversityofCaliforniaLosAngelesAIDSInstitute,UniversityofCaliforniaLosAngelesSchoolofMedicine,Los Angeles,California,UnitedStatesofAmerica,3DepartmentofCancerBiology,LernerResearchInstitute,ClevelandClinic,Cleveland,Ohio,UnitedStatesofAmerica Abstract Xenotropicmurineleukemiavirus(MLV)-relatedvirus(XMRV)isanewhumanretrovirusassociatedwithprostatecancerand chronicfatiguesyndrome.ThecausalrelationshipofXMRVinfectiontohumandiseaseandthemechanismofpathogenicity havenotbeenestablished.Duringretrovirusreplication,integrationofthecDNAcopyoftheviralRNAgenomeintothe host cellchromosomeis anessential step andinvolvescoordinatedjoining ofthetwoends ofthelinear viralDNAinto staggered sites on target DNA. Correct integration produces proviruses that are flanked by a short direct repeat, which variesfrom4to6bpamongtheretrovirusesbutisinvariantforeachparticularretrovirus.Uncoordinatedjoiningofthetwo viral DNA ends into target DNA can cause insertions, deletions, or other genomic alterations at the integration site. To determinethefidelityofXMRVintegration,cellsinfectedwithXMRVwereclonallyexpandedandDNAsequencesatthe viral-host DNA junctions were determined and analyzed. We found that a majority of the provirus ends were correctly processedandflankedbya4-bpdirectrepeatofhostDNA.AweakconsensussequencewasalsodetectedattheXMRV integrationsites.WeconcludethatintegrationofXMRVDNAinvolvesacoordinatedjoiningoftwoviralDNAendsthatare spaced4bpapartonthetargetDNAandproceedswithhighfidelity. Citation: Kim S, Rusmevichientong A, Dong B, Remenyi R, Silverman RH, et al. (2010) Fidel