李文辉

2020年11月12日，李文辉凭借其在推动乙肝科研和治疗方面做出的杰出贡献，荣获全球乙肝研究和治疗领域最高奖——巴鲁克·布隆伯格奖 。

本实验室的主要研究兴趣为囊膜病毒侵入细胞及相关过程的分子机制。病毒侵入细胞起始于与细胞表面受体的结合。围绕这一过程，我们希望探索：病毒细胞受体分子的识别；病毒受体是如何介导病毒感染的；其它胞内因子是如何参与病毒侵入的；病毒蛋白是如何进行免疫逃逸的；如何有效地抑制病毒的感染，等。我们综合运用病毒学，生物化学，化学生物学等多学科方法，以回答上述问题。这些研究将有利于深化对于病毒基本生物学，及病毒与感染宿主相互作用的认识与理解，并且有助于开发有效的抗病毒制剂及新型疫苗。

乙型肝炎是危害人类健康的严重传染病，是导致肝硬化、肝癌的重要病因。我们最近成功地发现并确认了人类乙型肝炎病毒，及其密切相关的丁型肝炎病毒感染肝细胞所必需的功能受体分子是肝细胞膜上的钠离子-牛磺胆酸-协同转运蛋白（NTCP）。这一重要发现为进一步深入研究乙肝病毒及相关致病机制打开了新的大门，并为研发新的药物和治疗手段提供了可能。

Ourlabtriestounderstandtheentrymechanismsofenvelopedviruses.Regardlessofthetypeofenvelopedvirus,theinitialstepofviralentryalwaysinvolvestheinteractionsbetweentheviralenvelopeprotein(s)andviralreceptor(s)onhostcells.Thequestionsthatwearemostlyinterestedinare:whatisthespecificcellularreceptorforavirus?Howdoesthereceptorcontributetoviralentry?Howdoestheviralentryproteinevadethehostimmuneresponse?Howcanviralinfectionbeinhibitedbyentryinhibitororhostimmunity.Weseektoidentifythereceptorsandelucidatetheentryprocessesofviralpathogensimportanttohumanhealth.Knowledgeofviralentrymechanismswilldeepenourunderstandingofbasicbiologyofvirusesandtheirhostcells,andoffernewopportunitiestodevelopmoreefficientinhibitorsagainsttheinfectionsandnewgenerationofviralvaccines.

HepatitisBvirus(HBV)infectionanditsassociatedcirrhosisandhepatocellularcarcinomacauseaboutonemilliondeathsannually.ThemolecularmechanismsbywhichHBVanditssatellitevirusHepatitisDvirus(HDV)infecthumanliverhavebeenelusive.Bytakingstate-of-the-artaffinitypurificationapproach,werecentlyidentifiedsodiumtaurocholatecotransportingpolypeptide(NTCP),aliverbileacidtransporter,asaspecificreceptorforHBVandHDV.NTCPbindstoacriticalreceptorbindingregionofviralenvelopeLproteinandcontributessubstantiallytotheefficiencyofHBVandHDVinfections.ThisfindingadvancesourunderstandingoftheHBVandHDVinfectionandmayleadtonewstrategiesforpreventionandtreatmentoftheseviralinfectionsandassociateddiseases.

2017年9月30日，当选2017年北京学者。

2020年11月12日，李文辉凭借其在推动乙肝科研和治疗方面做出的杰出贡献，荣获全球乙肝研究和治疗领域最高奖——巴鲁克·布隆伯格奖。这是迄今为止我国科学家首次获此殊荣 。

1.

LiW,SuiJ,HuangIC,KuhnJH,RadoshitzkySR,MarascoWA,ChoeH,FarzanM.TheSproteinsofhumancoronavirusNL63andsevereacuterespiratorysyndromecoronavirusbindoverlappingregionsofACE2.Virology.2007;doi:10.1016/j.virol.2007.04.035

2.

RadoshitzkySR,AbrahamJ,SpiropoulouCF,KuhnJH,NguyenD,LiW,NagelJ,SchmidtPJ,NunbergJH,AndrewsNC,FarzanM,ChoeH.Transferrinreceptor1isacellularreceptorforNewWorldhaemorrhagicfeverarenaviruses.Nature.2007;446(7131):92-6.

3.

KuhnJH,LiW,RadoshitzkySR,ChoeH,FarzanM.Severeacuterespiratorysyndromecoronavirusentryasatargetofantiviraltherapies.AntiviralTherapy.2007,12:639-650review

4.

LiF,BerardiM,LiW,FarzanM,DormitzerPR,HarrisonSC.Conformationalstatesofthesevereacuterespiratorysyndromecoronavirusspikeproteinectodomain.JVirol.2006,80(14):6794-800.

5.

HeY,LiJ,LiW,LustigmanS,FarzanM,JiangS.Cross-neutralizationofhumanandpalmcivetsevereacuterespiratorysyndromecoronavirusesbyantibodiestargetingthereceptor-bindingdomainofspikeprotein.JImmunol.2006,176(10):6085-92.

6.

LiW,WongSK,LiF,KuhnJH,HuangIC,ChoeH,FarzanM.Animaloriginsofthesevereacuterespiratorysyndromecoronavirus:insightfromACE2-S-proteininteractions.JVirol.2006,80(9):4211-9review

7.

KuhnJH,RadoshitzkySR,GuthAC,WarfieldKL,LiW,VincentMJ,TownerJS,NicholST,BavariS,ChoeH,AmanMJ,FarzanM.Conservedreceptor-bindingdomainsofLakeVictoriamarburgvirusandZaireebolavirusbindacommonreceptor.JBiolChem.2006,281(23):15951-8.

8.

HuangIC,BoschBJ,LiF,LiW,LeeKH,GhiranS,VasilievaN,DermodyTS,HarrisonSC,DormitzerPR,FarzanM,RottierPJ,ChoeH.SARScoronavirus,butnothumancoronavirusNL63,utilizescathepsinLtoinfectACE2-expressingcells.JBiolChem.2006,281(6):3198-203.

9.

ZhangL,ZhangF,YuW,HeT,YuJ,YiCE,BaL,LiW,FarzanM,ChenZ,YuenKY,HoD.AntibodyresponsesagainstSARScoronavirusarecorrelatedwithdiseaseoutcomeofinfectedindividuals.JMedVirol.2006,78(1):1-8.

10.

LiF,LiW,FarzanM,HarrisonSC.StructureofSARScoronavirusspikereceptor-bindingdomaincomplexedwithreceptor.Science.2005,309(5742):1864-8.Commentsinscience.2005,16;309(5742):1822-3.

11.

SuiJ,LiW,RobertsA,MatthewsLJ,MurakamiA,VogelL,WongSK,SubbaraoK,FarzanM,MarascoWA.Evaluationofhumanmonoclonalantibody80Rforimmunoprophylaxisofsevereacuterespiratorysyndromebyananimalstudy,epitopemapping,andanalysisofspikevariants.JVirol.2005,79(10):5900-6.

12.

LiW,ZhangC,SuiJ,KuhnJH,MooreMJ,LuoS,WongSK,HuangIC,XuK,VasilievaN,MurakamiA,HeY,MarascoWA,GuanY,ChoeH,FarzanM.ReceptorandviraldeterminantsofSARS-coronavirusadaptationtohumanACE2.EMBOJ.2005,24(8):1634-43.

13.

SuiJ,LiW,MurakamiA,TaminA,MatthewsLJ,WongSK,MooreMJ,TallaricoAS,OlurindeM,ChoeH,AndersonLJ,BelliniWJ,FarzanM,MarascoWA.Potentneutralizationofsevereacuterespiratorysyndrome(SARS)coronavirusbyahumanmAbtoS1proteinthatblocksreceptorassociation.ProcNatlAcadSciUSA.2004,101(8):2536-41.

14.

WongSK,LiW,MooreMJ,ChoeH,FarzanM.A193-aminoacidfragmentoftheSARScoronavirusSproteinefficientlybindsangiotensin-convertingenzyme2.JBiolChem.2004,279(5):3197-201.

15.

MooreMJ,DorfmanT,LiW,WongSK,LiY,KuhnJH,CoderreJ,VasilievaN,HanZ,GreenoughTC,FarzanM,ChoeH.Retrovirusespseudotypedwiththesevereacuterespiratorysyndromecoronavirusspikeproteinefficientlyinfectcellsexpressingangiotensin-convertingenzyme2.JVirol.2004;78(19):10628-35.

16.

LiW,MooreMJ,VasilievaN,SuiJ,WongSK,BerneMA,SomasundaranM,SullivanJL,LuzuriagaK,GreenoughTC,ChoeH,FarzanM.Angiotensin-convertingenzyme2isafunctionalreceptorfortheSARScoronavirus.Nature.2003,426(6965):450-4.CommentinCell.2003,115(6):652-3

17.

ChoeH,LiW,WrightPL,VasilievaN,VenturiM,HuangCC,GrundnerC,DorfmanT,ZwickMB,WangL,RosenbergES,KwongPD,BurtonDR,RobinsonJE,SodroskiJG,FarzanM.TyrosinesulfationofhumanantibodiescontributestorecognitionoftheCCR5bindingregionofHIV-1gp120.Cell.2003,114(2):161-70.CommentinCell.2003,114(2):147-8.

18.

FarzanM,ChungS,LiW,VasilievaN,WrightPL,SchnitzlerCE,MarchioneRJ,GerardC,GerardNP,SodroskiJ,ChoeH.Tyrosine-sulfatedpeptidesfunctionallyreconstituteaCCR5variantlackingacriticalamino-terminalregion.JBiolChem.2002,277(43):40397-402.

19.

LiW,ZhangY,SuiJ,WangS.CombinedimmunizationofDNAvaccineandreplication-defectiverecombinantadenovirusbearingrabiesglycoproteingeneinducesimmuneresponseagainstrabiesvirus.ChineseJournalofMicrobiologyandImmunology,2002,22(4):403-406

20.

SuiJ,LiW,JiangX,HeY,SongZ.HighlyEfficientExpressionandFunctionalStudiesofAnAnti-KG1aCellscFv5C1derivedfromPhageDisplayAntibodyLibrary.ChineseJournalofMicrobiologyandImmunology.2001,21(4):437~441

21.

LiW,ZhangY,WangS,LiuL.Immuneresponseofmiceagainstreplication-defectiverecombinantadenoviruscontainingglycoproteingeneofrabies3aGstrain.ChineseJournalofExperimentalandClinicalVirology,2001,15(1):35-39

22.

LiW,WangS,ZhangY,LiuL.ConstructionofclonedrecombinantadenovirusgenomebyhomologousrecombinationinEscherichiacoli.ChineseJournalofBiochemistryandMolecularBiology,2000,16(3):346-351

23.

ShenX,XieY,LiW.ConstructionofrecombinantHBVpreS2-SPichiapastoris.ProgressinMicrobiologyandImmunology,1999,27(1):14-18

妻子：隋建华，北京生命科学研究所研究员，生物制品中心和抗体中心主任。[4-5]