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.
Previously, 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.
Geldmacher
Astrid
A
Institute of Virology, Charité School of Medicine, D-10098 Berlin, Germany.
Skrastina
Dace
D
Petrovskis
Ivars
I
Borisova
Galina
G
Berriman
John A
JA
Roseman
Alan M
AM
Crowther
R Anthony
RA
Fischer
Jan
J
Musema
Shamil
S
Gelderblom
Hans R
HR
Lundkvist
Ake
A
Renhofa
Regina
R
Ose
Velta
V
Krüger
Detlev H
DH
Pumpens
Paul
P
Ulrich
Rainer
R
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D003429:Cross Reactions; D020285:Cryoelectron Microscopy; D005260:Female; D006476:Orthohantavirus / Q000145:classification / Q000276:immunology*; D018778:Hantavirus Infections / Q000517:prevention & control; D006512:Hepatitis B Core Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
D000914:Antibodies, Viral; D006512:Hepatitis B Core Antigens; D019590:Nucleocapsid Proteins; D011993:Recombinant Fusion Proteins; D014765:Viral Vaccines