This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kaverin, N. V.
Right arrow Articles by Webster, R. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kaverin, N. V.
Right arrow Articles by Webster, R. G.

 Previous Article  |  Next Article 

Journal of Virology, December 2007, p. 12911-12917, Vol. 81, No. 23
0022-538X/07/$08.00+0     doi:10.1128/JVI.01522-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Epitope Mapping of the Hemagglutinin Molecule of a Highly Pathogenic H5N1 Influenza Virus by Using Monoclonal Antibodies{triangledown}

Nikolai V. Kaverin,1 Irina A. Rudneva,1 Elena A. Govorkova,1,2 Tatyana A. Timofeeva,1 Aleksandr A. Shilov,1 Konstantin S. Kochergin-Nikitsky,1 Piotr S. Krylov,1 and Robert G. Webster2,3*

D. I. Ivanovsky Institute of Virology, 123098 Moscow, Russia,1 Department of Infectious Diseases, St. Jude Children's Research Hospital,2 Department of Pathology, University of Tennessee, Memphis, Tennessee 381053

Received 11 July 2007/ Accepted 9 September 2007

We mapped the hemagglutinin (HA) antigenic epitopes of a highly pathogenic H5N1 influenza virus on the three-dimensional HA structure by characterizing escape mutants of a recombinant virus containing A/Vietnam/1203/04 (H5N1) {Delta}HA and neuraminidase genes in the genetic background of A/Puerto Rico/8/34 (H1N1) virus. The mutants were selected with a panel of eight anti-HA monoclonal antibodies (MAbs), seven to A/Vietnam/1203/04 (H5N1) virus and one to A/Chicken/Pennsylvania/8125/83 (H5N2) virus, and the mutants’ HA genes were sequenced. The amino acid changes suggested three MAb groups: four MAbs reacted with the complex epitope comprising parts of the antigenic site B of H3 HA and site Sa of H1 HA, two MAbs reacted with the epitope corresponding to the antigenic site A in H3 HA, and two MAbs displayed unusual behavior: each recognized amino acid changes at two widely separate antigenic sites. Five changes were detected in amino acid residues not previously reported as changed in H5 escape mutants, and four others had substitutions not previously described. The HA antigenic structure differs substantially between A/Vietnam/1203/04 (H5N1) virus and the low-pathogenic A/Mallard/Pennsylvania/10218/84 (H5N2) virus we previously characterized (N. V. Kaverin et al., J. Gen. Virol. 83:2497-2505, 2002). The hemagglutination inhibition reactions of the MAbs with recent highly pathogenic H5N1 viruses were consistent with the antigenic-site amino acid changes but not with clades and subclades based on H5 phylogenetic analysis. These results provide information on the recognition sites of the MAbs widely used to study H5N1 viruses and demonstrate the involvement of the HA antigenic sites in the evolution of highly pathogenic H5N1 viruses, findings that can be critical for characterizing pathogenesis and vaccine design.

* Corresponding author. Mailing address: Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 North Lauderdale St., Memphis, TN 38105-2794. Phone: (901) 495-3400. Fax: (901) 523-2622. E-mail: robert.webster{at}stjude.org

{triangledown} Published ahead of print on 19 September 2007.

Journal of Virology, December 2007, p. 12911-12917, Vol. 81, No. 23
0022-538X/07/$08.00+0     doi:10.1128/JVI.01522-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Reed, M. L., Yen, H.-L., DuBois, R. M., Bridges, O. A., Salomon, R., Webster, R. G., Russell, C. J. (2009). Amino Acid Residues in the Fusion Peptide Pocket Regulate the pH of Activation of the H5N1 Influenza Virus Hemagglutinin Protein. J. Virol. 83: 3568-3580 [Abstract] [Full Text]  
  • Prabhu, N., Prabakaran, M., Ho, H.-T., Velumani, S., Qiang, J., Goutama, M., Kwang, J. (2009). Monoclonal Antibodies against the Fusion Peptide of Hemagglutinin Protect Mice from Lethal Influenza A Virus H5N1 Infection. J. Virol. 83: 2553-2562 [Abstract] [Full Text]  
  • Kim, J.-K., Seiler, P., Forrest, H. L., Khalenkov, A. M., Franks, J., Kumar, M., Karesh, W. B., Gilbert, M., Sodnomdarjaa, R., Douangngeun, B., Govorkova, E. A., Webster, R. G. (2008). Pathogenicity and Vaccine Efficacy of Different Clades of Asian H5N1 Avian Influenza A Viruses in Domestic Ducks. J. Virol. 82: 11374-11382 [Abstract] [Full Text]  
  • Kosakovsky Pond, S. L., Poon, A. F.Y., Leigh Brown, A. J., Frost, S. D.W. (2008). A Maximum Likelihood Method for Detecting Directional Evolution in Protein Sequences and Its Application to Influenza A Virus. Mol Biol Evol 25: 1809-1824 [Abstract] [Full Text]  
  • Kongchanagul, A., Suptawiwat, O., Kanrai, P., Uiprasertkul, M., Puthavathana, P., Auewarakul, P. (2008). Positive selection at the receptor-binding site of haemagglutinin H5 in viral sequences derived from human tissues. J. Gen. Virol. 89: 1805-1810 [Abstract] [Full Text]  
  • Wu, W. L., Chen, Y., Wang, P., Song, W., Lau, S.-Y., Rayner, J. M., Smith, G. J. D., Webster, R. G., Peiris, J. S. M., Lin, T., Xia, N., Guan, Y., Chen, H. (2008). Antigenic Profile of Avian H5N1 Viruses in Asia from 2002 to 2007. J. Virol. 82: 1798-1807 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»