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Journal of Virology, August 2005, p. 10003-10012, Vol. 79, No. 15
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.15.10003-10012.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Chimeric Influenza Virus Hemagglutinin Proteins Containing Large Domains of the Bacillus anthracis Protective Antigen: Protein Characterization, Incorporation into Infectious Influenza Viruses, and Antigenicity

Zhu-Nan Li,1 Scott N. Mueller,1 Ling Ye,1 Zhigao Bu,2 Chinglai Yang,1 Rafi Ahmed,1 and David A. Steinhauer1*

Department of Microbiology and Immunology, Emory University School of Medicine, Rollins Research Center, 1510 Clifton Road, Atlanta, Georgia 30322,1 National Key Laboratory Veterinary Biotechnology, Harbin Veterinary Research Institute, Harbin, People's Republic of China2

Received 20 January 2005/ Accepted 14 April 2005

Large polypeptides of the Bacillus anthracis protective antigen (PA) were inserted into an influenza A virus hemagglutinin glycoprotein (HA), and the chimeric proteins were functionally characterized and incorporated into infectious influenza viruses. PA domain 1', the region responsible for binding to the other toxin components, the lethal factor and edema factor, and domain 4, the receptor binding domain (RBD), were inserted at the C-terminal flank of the HA signal peptide and incorporated into the HA1 subunit of HA. The chimeric proteins, designated as LEF/HA (90 amino acid insertion) and RBD/HA (140 amino acid insertion), were initially analyzed following expression using recombinant vaccinia viruses. Both chimeric proteins were shown to display functional phenotypes similar to that of the wild-type HA. They transport to the cell surface, can be cleaved into the HA1 and HA2 subunits by trypsin to activate membrane fusion potential, are able to undergo the low-pH-induced conformational changes required for fusion, and are capable of inducing the fusion process. We were also able to generate recombinant influenza viruses containing the chimeric RBD/HA and LEF/HA genes, and the inserted PA domains were maintained in the HA gene segments following several passages in MDCK cells or embryonated chicken eggs. Furthermore, DNA immunization of mice with plasmids that express the chimeric RBD/HA and LEF/HA proteins, and the recombinant viruses containing them, induced antibody responses against both the HA and PA components of the protein. These approaches may provide useful tools for vaccines against anthrax and other diseases.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Emory University School of Medicine, Rollins Research Center, 1510 Clifton Road, Atlanta, GA 30322. Phone: (404) 712-8542. Fax: (404) 727-3659. E-mail: steinhauer{at}microbio.emory.edu.

Journal of Virology, August 2005, p. 10003-10012, Vol. 79, No. 15
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.15.10003-10012.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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