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Journal of Virology, July 2003, p. 8031-8038, Vol. 77, No. 14
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.14.8031-8038.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Generation of Influenza A Viruses with Chimeric (Type A/B) Hemagglutinins

Taisuke Horimoto,^1* Ayato Takada,¹ Kiyoko Iwatsuki-Horimoto,¹ Masato Hatta,² Hideo Goto,¹ and Yoshihiro Kawaoka^1,2,3*

Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639,¹ Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Saitama 332-0012, Japan,³ Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 53706²

Received 3 February 2003/ Accepted 17 April 2003

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 10⁵ 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.

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* Corresponding author. Mailing address: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan. Phone: 81 3 5449 5504. Fax: 81 3 5449 5408. E-mail for T. Horimoto: horimoto{at}ims.u-tokyo.ac.jp E-mail for Y. Kawaoka kawaoka{at}ims.u-tokyo.ac.jp.

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Journal of Virology, July 2003, p. 8031-8038, Vol. 77, No. 14
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.14.8031-8038.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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