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 Abed, Y.
Right arrow Articles by Boivin, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Abed, Y.
Right arrow Articles by Boivin, G.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, February 2005, p. 556-559, Vol. 49, No. 2
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.2.556-559.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Generation and Characterization of Recombinant Influenza A (H1N1) Viruses Harboring Amantadine Resistance Mutations

Yacine Abed, Nathalie Goyette, and Guy Boivin*

<[ERROR]zaff;1[ERROR]>Research Center in Infectious Diseases of the CHUQ-CHUL and Laval University, Québec City, Canada

Received 4 June 2004/ Returned for modification 15 July 2004/ Accepted 14 October 2004

The emergence of resistance to amantadine in influenza A viruses has been shown to occur rapidly during treatment as a result of single-amino-acid substitutions at position 26, 27, 30, 31, or 34 within the transmembrane domain of the matrix-(M)-2 protein. In this study, reverse genetics was used to generate and characterize recombinant influenza A (H1N1) viruses harboring L26F, V27A, A30T, S31N, G34E, and V27A/S31N mutations in the M2 gene. In plaque reduction assays, all mutations conferred amantadine resistance, with drug concentrations resulting in reduction of plaque number by 50% (IC50s) 154- to 3,300-fold higher than those seen for the wild type (WT). M2 mutants had no impairment in their replicative capacities in vitro on the basis of plaque size and replication kinetics experiments. In addition, all mutants were at least as virulent as the WT in experimentally infected mice, with the highest mortality rate being obtained with the recombinant harboring a double V27A/S31N mutation. These findings could help explain the frequent emergence and transmission of amantadine-resistant influenza viruses during antiviral pressure in the clinical setting.

* Corresponding author. Mailing address: CHUQ-CHUL, room RC-709, 2705 Blvd. Laurier Sainte-Foy, Québec, Canada G1V 4G2. Phone: (418) 654 2705. Fax: (418) 654 2715. E-mail: Guy.Boivin{at}crchul.ulaval.ca.

Antimicrobial Agents and Chemotherapy, February 2005, p. 556-559, Vol. 49, No. 2
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.2.556-559.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Furuse, Y., Suzuki, A., Kishi, M., Nukiwa, N., Shimizu, M., Sawayama, R., Fuji, N., Oshitani, H. (2010). Occurrence of Mixed Populations of Influenza A Viruses That Can Be Maintained through Transmission in a Single Host and Potential for Reassortment. J. Clin. Microbiol. 48: 369-374 [Abstract] [Full Text]  
  • Furuse, Y., Suzuki, A., Oshitani, H. (2009). Large-Scale Sequence Analysis of M Gene of Influenza A Viruses from Different Species: Mechanisms for Emergence and Spread of Amantadine Resistance. Antimicrob. Agents Chemother. 53: 4457-4463 [Abstract] [Full Text]  
  • Smee, D. F., Hurst, B. L., Wong, M.-H., Bailey, K. W., Morrey, J. D. (2009). Effects of Double Combinations of Amantadine, Oseltamivir, and Ribavirin on Influenza A (H5N1) Virus Infections in Cell Culture and in Mice. Antimicrob. Agents Chemother. 53: 2120-2128 [Abstract] [Full Text]  
  • Krumbholz, A., Schmidtke, M., Bergmann, S., Motzke, S., Bauer, K., Stech, J., Durrwald, R., Wutzler, P., Zell, R. (2009). High prevalence of amantadine resistance among circulating European porcine influenza A viruses. J. Gen. Virol. 90: 900-908 [Abstract] [Full Text]  
  • Wasilenko, J. L., Lee, C. W., Sarmento, L., Spackman, E., Kapczynski, D. R., Suarez, D. L., Pantin-Jackwood, M. J. (2008). NP, PB1, and PB2 Viral Genes Contribute to Altered Replication of H5N1 Avian Influenza Viruses in Chickens. J. Virol. 82: 4544-4553 [Abstract] [Full Text]  
  • Weinstock, D. M., Zuccotti, G. (2006). Adamantane Resistance in Influenza A. JAMA 295: 934-936 [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»