Current Topics in Microbiology and Immunology Volume 343 Series Editors Klaus Aktories Albert-Ludwigs-Universita¨tFreiburg,Medizinische Fakulta¨t, Institutfu¨rExperimentelle undKlinischePharmakologie undToxikologie,Abt. I,Albertstr.25, 79104Freiburg, Germany Richard W.Compans EmoryUniversity Schoolof Medicine, Department ofMicrobiologyand Immunology, 3001Rollins Research Center,Atlanta, GA30322, USA Max D.Cooper Department of PathologyandLaboratory Medicine, GeorgiaResearch Alliance, EmoryUniversity, 1462Clifton Road,Atlanta, GA30322, USA Yuri Y.Gleba ICONGenetics AG,Biozentrum Halle,Weinbergweg 22, Halle 6120,Germany Tasuku Honjo Department of Medical Chemistry, KyotoUniversity, Facultyof Medicine, Yoshida, Sakyo-ku,Kyoto606-8501, Japan Hilary Koprowski ThomasJefferson University, Department ofCancer Biology, BiotechnologyFoundation Laboratories, 1020Locust Street,Suite M85JAH, Philadelphia, PA 19107-6799,USA BernardMalissen Centre d’Immunologiede Marseille-Luminy, ParcScientifique deLuminy, Case906, Marseille Cedex 9 13288, France FritzMelchers Max PlanckInstituteforInfection Biology, Charite´platz1, 10117Berlin,Germany Michael B.A. Oldstone Department of Neuropharmacology, Division ofVirology, The ScrippsResearch Institute, 10550N.TorreyPines, La Jolla, CA 92037,USA SjurOlsnes Department of Biochemistry, InstituteforCancer Research,The Norwegian Radium Hospital,Montebello 0310Oslo, Norway Herbert W.“Skip”Virgin Washington UniversitySchool ofMedicine, Pathologyand Immunology,UniversityBox 8118,660South Euclid Avenue, SaintLouis,Missouri 63110,USA Peter K.Vogt The ScrippsResearch Institute, Dept.of Molecular& Exp.Medicine, Division of Oncovirology, 10550N.TorreyPines. BCC-239,La Jolla, CA 92037,USA Current Topics in Microbiology and Immunology Previously published volumes Further volumes can be found at springer.com Vol.317:Dessain,ScottK.(Ed.): Vol.330:DianeE.Griffin;MichaelB.A. HumanAntibodyTherapeuticsforViralDisease. Oldstone(Eds.):Measles2009. 2007.XI,202pp.ISBN978-3-540-72144-4 ISBN978-3-540-70616-8 Vol.318:Rodriguez,Moses(Ed.): Vol.331:Villiers,E.M.de(Eds): AdvancesinMultipleSclerosisand TTViruses.2009.ISBN978-3-540-70917-8 ExperimentalDemyelinatingDiseases.2008. XIV,376pp.ISBN978-3-540-73679-9 Vol.332:KarasevA.(Ed.): PlantproducedMicrobialVaccines.2009. Vol.319:Manser,Tim(Ed.): ISBN978-3-540-70857-5 SpecializationandComplementation ofHumoralImmuneResponsestoInfection. 2008.XII,174pp.ISBN978-3-540-73899-2 Vol.333:RichardW.Compans; WalterA.Orenstein(Eds): Vol.320:Paddison,PatrickJ.; VaccinesforPandemicInfluenza.2009. Vogt,PeterK.(Eds.):RNAInterference.2008. 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Johnson Editor Cell Entry by Non-Enveloped Viruses Editor Prof.JohnE.Johnson ScrippsResearchInstitute Dept.MolecularBiology N.TorreyPinesRd.10550 92037LaJollaCalifornia USA [email protected] ISSN0070-217X ISBN:978-3-642-13331-2 e-ISBN:978-3-642-13332-9 DOI10.1007/978-3-642-13332-9 SpringerHeidelbergDordrechtLondonNewYork LibraryofCongressControlNumber:2010935081 #Springer-VerlagBerlinHeidelberg2010 Thisworkissubjecttocopyright.Allrightsarereserved,whetherthewholeorpartofthematerialis concerned,specificallytherightsoftranslation,reprinting,reuseofillustrations,recitation,broadcasting, reproductiononmicrofilmorinanyotherway,andstorageindatabanks.Duplicationofthispublication orpartsthereofispermittedonlyundertheprovisionsoftheGermanCopyrightLawofSeptember9, 1965,initscurrentversion,andpermissionforusemustalwaysbeobtainedfromSpringer.Violations areliabletoprosecutionundertheGermanCopyrightLaw. Theuseofgeneraldescriptivenames,registerednames,trademarks,etc.inthispublicationdoesnot imply,evenintheabsenceofaspecificstatement,thatsuchnamesareexemptfromtherelevantprotec- tivelawsandregulationsandthereforefreeforgeneraluse. Coverdesign:WMXDesignGmbH,Heidelberg,Germany Printedonacid-freepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) Preface Thisvolumecoversnon-envelopedvirusesandtheircellularentryanddescribesthe mostthoroughlyinvestigatedmembersinthiscategory.Itisanappropriatetimefor suchacomprehensivereview,sincestructural,biochemical,andcellbiologicalinves- tigationshaveadvancedtoapointwherestrategiesforentry,particletransitions,and membranesbreachedarereasonablywelldefinedformostmembers.Weanticipate that the information presented here will be of lasting relevance. We also hope that thisvolumewillstimulateadditionalstudiesthatcontributetoanelucidationofthe moleculardetailsofmembranedisruptionandgenometranslocationforthistypeof virus.Thevolumeisorganizedaccordingtoviralfamilies,withchaptersfirstaddres- singssRNAanddsRNAviruses,thenssDNAviruses,andfinallydsDNAviruses. Although the number of gene products and the chemical nature of the genome varywidelyamongtheseviruses,thereareunifyingthemes.Alltheseviruseshave icosahedralsymmetry,andallhaveatleastonegeneproductintheircapsidswith theviraljellyrollfold.Thefoldisabeta-sandwichwithuniquetopology(Chapman and Liljas 2003) found predominantly in viral capsid proteins. This is a clear indication that these viruses have a common ancestor, but the evolutionary rela- tionshipamongthevirusesisimpossibletoestablish,sincevirusesundergoexcep- tionallevelsofhorizontalgeneexchange.Alltheviruseshaveasinglejellyrollin their gene products, except adenovirus that has two jellyrolls fused together in a single gene encoding the major capsid protein. The jellyroll topology relates the virusesdiscussedheretonon-enveloped,icosahedralvirusesthatinfectbacteriaand plants. Indeed, the fused jellyrolls of adenovirus have appeared in dsDNA virus structures infecting bacteria and archea, although the latter viruses have internal envelopes(Bamfordetal.2005). All animal viruses must breach a membrane to deliver their genome or, for dsRNA viruses, the particle that synthesizes the genome, into the cell cytoplasm. DNAvirusesmust,inaddition,getthegenomeintothenucleus.Envelopedviruses fuse their envelope membrane with a cellular membrane, creating a portal to transportthecontentswithintheviralenvelopeintothecytoplasm.Themechanism forthiseventhasbeenextensivelyinvestigatedandisreasonablywellunderstood (Harrison2008).Theprocessisinitiatedbytheexposureofaviral“fusionpeptide” v vi Preface whenthevirusisintheproperlocationforgenomedelivery.Changesinthevirion structure, often initiated by change in pH, lead to the exposure of the normally sequestered hydrophobic peptide. The fusion peptide anchors the viral membrane intothecellularmembrane,initiatingthefusionprocess. As discussed in many of the chapters in this volume, non-enveloped viruses expose“lyticpeptides”thatinteractwithmembranesandfacilitategenomedelivery through a mechanism that is yet to be determined (Banerjee and Johnson 2008). Generation of this peptide appears to be the result of convergent evolution, since most non-enveloped viruses have a novel mechanism for its origin. A common featurefoundinnoda-(Odegardetal,thisvolume)andpicornaviruses(Tuthilletal, thisvolume)istheautocatalyticcleavageoftheviralsubunittocreateacovalently independent,butparticle-associated,polypeptide.TheC-terminal44-residuepoly- peptide of Flock House Virus is transiently exposed in a pH-dependent manner. MaximumexposureandlysisofliposomesinvitrooccursatpH6.5.Likewise,vp4 ofpicornavirusesresultsfrompost-assembly,autocatalyticcleavage,remainsasso- ciatedwiththeparticle,andistransientlyexposed.TheN-terminiofthepicornavi- rus polypeptides are myristoylated, and this moiety targets them to membranes. Broad-spectrumantiviralactivityinpicornaviruses isassociated with smallmole- culesthatinhibittherequireddynamiccharacteroftheparticle,preventinggenome translocationacrossacellularmembrane. A 675-residue capsid gene product in the dsRNA orthoreovirus, m1, has a myristoylated N-terminus and undergoes an auto-catalytic cleavage between resi- due42and43.AvarietyofdatadiscussedinDanthietal.inthisvolumeimplicate thispolypeptideinmembranetranslocationoftheentireinnercoreofreovirus.The dsRNArotavirusuncoversitsmembraneactiveregionthroughthetrypsincleavage oftheVP4spikeproteins(BakerandPrasad,thisvolume).VP8andVP5*arethe resultantcleavageproducts,andwhenVP8dissociatesfromVP5*,trimerichydro- phobicloopsareexposedthatinteractdirectlywiththetargetmembrane.Vp5*then undergoesadramaticconformational changethatdraws thetarget membrane into theproximityoftheinnercore. The ssDNA parvoviruses (Parrish, this volume) do not have a lytic peptide to alter host cell membranes. This virus group has a phospholipase A2 activity associatedwithit,butlikemanyothernon-envelopedviruses,thisactivityisonly activatedaftertheparticleshaveenteredtheendosomeandtheN-terminalresidues oftheVp1capsidproteinareexposedthrough5-foldaxes.Regionsofthisportion of the capsid are also thought to have nuclear localization signals. Polyomavirus has a dsDNA genome, and the particle travels in the endosome all the way to the endoplasmic reticulum where enzymes resident there induce the exposure of the hydrophobicVp2proteinthatmediatesparticletranslocationfromtheER(Tsaiand Qian,thisvolume).Finally,thedsDNAadenovirusdevotesanentiregeneproduct tothetaskofmembranetranslocation(Smithetal,thisvolume).Vp6iscomposed of residues 34–239 in the virion following its processing during assembly by a virally encoded protease. It is released into the endosomic membrane during particledisassemblywithintheendosome,facilitatingthereleaseofanucleoprotein complexthatisthentargetedtothenucleus. Preface vii Thediscussionabovehighlightstwoofthenumerousfeaturesdescribedindetail inthesechaptersandindicatestheintriguingassortmentofdivergenceandconver- genceassociatedwiththeevolutionofnon-envelopedvirusparticles.Thereaderof these chapters will be rewarded with a state-of-the-art description of the structure andfunctionofthisveryimportantclassofvirusesandmaywellbestimulatedto addtothisdevelopingstory. Summer2010 JohnE.Johnson PeterK.Vogt References Bamford DH, Grimes JM, Stuart DI (2005) What does structure tell us about virus evolution? CurrOpinStructBiol15:655–663 BanerjeeM,JohnsonJE(2008)Activation,exposureandpenetrationofvirallyencoded,mem- brane-activepolypeptidesduringnon-envelopedvirusentry.CurrProteinPeptSci9:16–27 ChapmanMS,LiljasL(2003)Structuralfoldsofviralproteins.AdvProteinChem64:125–196 HarrisonSC(2008)Viralmembranefusion.NatStructMolBiol15:690–698 . Contents FlockHouseVirus:AModelSystemforUnderstandingNon-Enveloped VirusEntryandMembranePenetration ..................................... 1 AmyOdegard,ManidipaBanerjee,andJohnE.Johnson TheCaliciviruses .............................................................. 23 UmeshKatpallyandThomasJ.Smith Picornaviruses ................................................................. 43 TobiasJ.Tuthill,ElisabettaGroppelli,JamesM.Hogle, andDavidJ.Rowlands FromTouchdowntoTranscription:TheReovirus CellEntryPathway ........................................................... 91 PranavDanthi,KristenM.Guglielmi,EvaKirchner,BernardoMainou, ThiloStehle,andTerenceS.Dermody RotavirusCellEntry ......................................................... 121 Matthew BakerandB.V.VenkataramPrasad StructuresandFunctionsofParvovirusCapsidsandtheProcess ofCellInfection .............................................................. 149 ColinR.Parrish CellularEntryofPolyomaviruses .......................................... 177 BillyTsaiandMengdingQian Adenovirus .................................................................... 195 JasonG.Smith,ChristopherM.Wiethoff,PhoebeL.Stewart, andGlenR.Nemerow Index .......................................................................... 225 ix