6533b825fe1ef96bd128200a

RESEARCH PRODUCT

An amino-terminal segment of hantavirus nucleocapsid protein presented on hepatitis B virus core particles induces a strong and highly cross-reactive antibody response in mice

ÅKe LundkvistÅKe LundkvistJohn A. BerrimanVelta OsePaul PumpensRainer UlrichR. Anthony CrowtherDetlev H. KrügerAlan M. RosemanJan Frederik FischerIvars PetrovskisRegina RenhofaAstrid GeldmacherDace SkrastinaGalina BorisovaShamil MusemaHans R. Gelderblom

subject

OrthohantavirusHepatitis B virusCryo-electron microscopyHantavirus InfectionsRecombinant Fusion ProteinsVirulenceCross Reactions030312 virologyAntibodies Viralmedicine.disease_causeCore antigenMice03 medical and health sciencesVirologymedicineAnimals030304 developmental biologyHantavirusNucleocapsid proteinchemistry.chemical_classificationHepatitis B virusMice Inbred BALB C0303 health sciencesbiologyCryoelectron MicroscopyViral VaccinesNucleocapsid ProteinsVirus-like particlesbiology.organism_classificationHepatitis B Core AntigensVirology3. Good healthAmino acidMice Inbred C57BLchemistrybiology.proteinFemalePuumala virusAntibodyHantavirus InfectionHantavirus

description

AbstractPreviously, we have demonstrated that hepatitis B virus (HBV) core particles tolerate the insertion of the amino-terminal 120 amino acids (aa) of the Puumala hantavirus nucleocapsid (N) protein. Here, we demonstrate that the insertion of 120 amino-terminal aa of N proteins from highly virulent Dobrava and Hantaan hantaviruses allows the formation of chimeric core particles. These particles expose the inserted foreign protein segments, at least in part, on their surface. Analysis by electron cryomicroscopy of chimeric particles harbouring the Puumala virus (PUUV) N segment revealed 90% T = 3 and 10% T = 4 shells. A map computed from T = 3 shells shows additional density splaying out from the tips of the spikes producing the effect of an extra shell of density at an outer radius compared with wild-type shells. The inserted Puumala virus N protein segment is flexibly linked to the core spikes and only partially icosahedrally ordered. Immunisation of mice of two different haplotypes (BALB/c and C57BL/6) with chimeric core particles induces a high-titered and highly cross-reactive N-specific antibody response in both mice strains.

yearjournalcountryeditionlanguage
2004-05-01Virology
https://doi.org/10.1016/j.virol.2004.02.022