Generation of influenza A viruses with chimeric (type A/B) hemagglutinins.
To gain insight into the intertypic incompatibility between type A and B influenza viruses, we focused on the hemagglutinin (HA) gene, systematically studying the compatibility of chimeric (type A/B) HAs with a type A genetic background. An attempt to generate a reassortant containing an intact type B HA segment in a type A virus background by reverse genetics was unsuccessful despite transcription of the type B HA segment by the type A polymerase complex. Although a type A virus with a chimeric HA segment comprising the entire coding sequence of the type B HA flanked by the noncoding sequence of the type A HA was viable, it replicated only marginally. Other chimeric viruses contained type A/B HAs possessing the type A noncoding region together with either the signal peptide or transmembrane/cytoplasmic region of type A virus or both, with the remaining regions derived from the type B HA. Each of these viruses grew to median tissue culture infectious doses of more than 10(5) per ml, but those with more type A HA regions replicated better, suggesting protein-protein interactions or increased HA segment incorporation into virions as contributing factors in the efficient growth of this series of viruses. All of these chimeric (A/B) HA viruses were attenuated in mice compared with wild-type A or B viruses. All animals intranasally immunized with a chimeric virus survived upon challenge with a lethal dose of wild-type type B virus. These results suggest a framework for the design of a novel live vaccine virus.
Horimoto
Taisuke
T
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan. horimoto@ims.u-tokyo.ac.jp
Takada
Ayato
A
Iwatsuki-Horimoto
Kiyoko
K
Hatta
Masato
M
Goto
Hideo
H
Kawaoka
Yoshihiro
Y
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002460:Cell Line; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D009981:Influenza B virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D007251:Influenza, Human / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014611:Vaccination; D014779:Virus Replication
D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011993:Recombinant Fusion Proteins