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
Services
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 Maines, T. R.
Right arrow Articles by Tumpey, T. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maines, T. R.
Right arrow Articles by Tumpey, T. M.

 Previous Article  |  Next Article 

Journal of Virology, September 2005, p. 11788-11800, Vol. 79, No. 18
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.18.11788-11800.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Avian Influenza (H5N1) Viruses Isolated from Humans in Asia in 2004 Exhibit Increased Virulence in Mammals

Taronna R. Maines,1 Xui Hua Lu,1 Steven M. Erb,1 Lindsay Edwards,1 Jeannette Guarner,2 Patricia W. Greer,2 Doan C. Nguyen,1 Kristy J. Szretter,1 Li-Mei Chen,1 Pranee Thawatsupha,3 Malinee Chittaganpitch,3 Sunthareeya Waicharoen,3 Diep T. Nguyen,4 Tung Nguyen,4 Hanh H. T. Nguyen,5 Jae-Hong Kim,6 Long T. Hoang,5 Chun Kang,7 Lien S. Phuong,4 Wilina Lim,8 Sherif Zaki,2 Ruben O. Donis,1 Nancy J. Cox,1 Jacqueline M. Katz,1 and Terrence M. Tumpey1*

Influenza Branch,1 Infectious Disease Pathology Activity, Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333,2 Thai National Influenza Center, National Institute of Health, Ministry of Public Health, Bangkok, Thailand 11000,3 National Center for Veterinary Diagnosis, Department of Animal Health, Ministry of Agriculture and Rural Development, Hanoi, Vietnam,4 National Institute of Hygiene and Epidemiology, Hanoi, Vietnam,5 National Veterinary Research and Quarantine Service, Anyang 430-824, Korea,6 Laboratory of Respiratory Viruses, Department of Viruses, Korean National Institute of Health, Seoul, Korea,7 Hong Kong National Influenza Center, Government Virus Unit, Kowloon, Hong Kong Special Administrative Region, China8

Received 9 April 2005/ Accepted 2 June 2005

The spread of highly pathogenic avian influenza H5N1 viruses across Asia in 2003 and 2004 devastated domestic poultry populations and resulted in the largest and most lethal H5N1 virus outbreak in humans to date. To better understand the potential of H5N1 viruses isolated during this epizootic event to cause disease in mammals, we used the mouse and ferret models to evaluate the relative virulence of selected 2003 and 2004 H5N1 viruses representing multiple genetic and geographical groups and compared them to earlier H5N1 strains isolated from humans. Four of five human isolates tested were highly lethal for both mice and ferrets and exhibited a substantially greater level of virulence in ferrets than other H5N1 viruses isolated from humans since 1997. One human isolate and all four avian isolates tested were found to be of low virulence in either animal. The highly virulent viruses replicated to high titers in the mouse and ferret respiratory tracts and spread to multiple organs, including the brain. Rapid disease progression and high lethality rates in ferrets distinguished the highly virulent 2004 H5N1 viruses from the 1997 H5N1 viruses. A pair of viruses isolated from the same patient differed by eight amino acids, including a Lys/Glu disparity at 627 of PB2, previously identified as an H5N1 virulence factor in mice. The virus possessing Glu at 627 of PB2 exhibited only a modest decrease in virulence in mice and was highly virulent in ferrets, indicating that for this virus pair, the K627E PB2 difference did not have a prevailing effect on virulence in mice or ferrets. Our results demonstrate the general equivalence of mouse and ferret models for assessment of the virulence of 2003 and 2004 H5N1 viruses. However, the apparent enhancement of virulence of these viruses in humans in 2004 was better reflected in the ferret.

* Corresponding author. Mailing address: Influenza Branch, Mail Stop G-16, DVRD, NCID, Centers for Disease Control and Prevention, 1600 Clifton Road, N.E., Atlanta, GA 30333. Phone: (404) 639-5444. Fax: (404) 639-2334. E-mail: tft9{at}cdc.gov.

Journal of Virology, September 2005, p. 11788-11800, Vol. 79, No. 18
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.18.11788-11800.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Shinya, K., Makino, A., Ozawa, M., Kim, J. H., Sakai-Tagawa, Y., Ito, M., Le, Q. M., Kawaoka, Y. (2009). Ostrich Involvement in the Selection of H5N1 Influenza Virus Possessing Mammalian-Type Amino Acids in the PB2 Protein. J. Virol. 83: 13015-13018 [Abstract] [Full Text]  
  • Cusick, M. F., Wang, S., Eckels, D. D. (2009). In Vitro Responses to Avian Influenza H5 by Human CD4 T Cells. J. Immunol. 183: 6432-6441 [Abstract] [Full Text]  
  • Shih, S.-R., Horng, J.-T., Poon, L. L. M., Chen, T.-C., Yeh, J.-Y., Hsieh, H.-P., Tseng, S.-N., Chiang, C., Li, W.-L., Chao, Y.-S., Hsu, J. T.-A. (2009). BPR2-D2 targeting viral ribonucleoprotein complex-associated function inhibits oseltamivir-resistant influenza viruses. J Antimicrob Chemother 0: dkp393v2-dkp393 [Abstract] [Full Text]  
  • Rodriguez, A., Perez-Gonzalez, A., Hossain, M. J., Chen, L.-M., Rolling, T., Perez-Brena, P., Donis, R., Kochs, G., Nieto, A. (2009). Attenuated Strains of Influenza A Viruses Do Not Induce Degradation of RNA Polymerase II. J. Virol. 83: 11166-11174 [Abstract] [Full Text]  
  • Lycett, S. J., Ward, M. J., Lewis, F. I., Poon, A. F. Y., Kosakovsky Pond, S. L., Brown, A. J. L. (2009). Detection of Mammalian Virulence Determinants in Highly Pathogenic Avian Influenza H5N1 Viruses: Multivariate Analysis of Published Data. J. Virol. 83: 9901-9910 [Abstract] [Full Text]  
  • Jackson, S., Van Hoeven, N., Chen, L.-M., Maines, T. R., Cox, N. J., Katz, J. M., Donis, R. O. (2009). Reassortment between Avian H5N1 and Human H3N2 Influenza Viruses in Ferrets: a Public Health Risk Assessment. J. Virol. 83: 8131-8140 [Abstract] [Full Text]  
  • Suzuki, K., Okada, H., Itoh, T., Tada, T., Mase, M., Nakamura, K., Kubo, M., Tsukamoto, K. (2009). Association of Increased Pathogenicity of Asian H5N1 Highly Pathogenic Avian Influenza Viruses in Chickens with Highly Efficient Viral Replication Accompanied by Early Destruction of Innate Immune Responses. J. Virol. 83: 7475-7486 [Abstract] [Full Text]  
  • Munster, V. J., de Wit, E., van den Brand, J. M. A., Herfst, S., Schrauwen, E. J. A., Bestebroer, T. M., van de Vijver, D., Boucher, C. A., Koopmans, M., Rimmelzwaan, G. F., Kuiken, T., Osterhaus, A. D. M. E., Fouchier, R. A. M. (2009). Pathogenesis and Transmission of Swine-Origin 2009 A(H1N1) Influenza Virus in Ferrets. Science 325: 481-483 [Abstract] [Full Text]  
  • Maines, T. R., Jayaraman, A., Belser, J. A., Wadford, D. A., Pappas, C., Zeng, H., Gustin, K. M., Pearce, M. B., Viswanathan, K., Shriver, Z. H., Raman, R., Cox, N. J., Sasisekharan, R., Katz, J. M., Tumpey, T. M. (2009). Transmission and Pathogenesis of Swine-Origin 2009 A(H1N1) Influenza Viruses in Ferrets and Mice. Science 325: 484-487 [Abstract] [Full Text]  
  • Belser, J. A., Wadford, D. A., Xu, J., Katz, J. M., Tumpey, T. M. (2009). Ocular Infection of Mice with Influenza A (H7) Viruses: a Site of Primary Replication and Spread to the Respiratory Tract. J. Virol. 83: 7075-7084 [Abstract] [Full Text]  
  • Nencioni, L., De Chiara, G., Sgarbanti, R., Amatore, D., Aquilano, K., Marcocci, M. E., Serafino, A., Torcia, M., Cozzolino, F., Ciriolo, M. R., Garaci, E., Palamara, A. T. (2009). Bcl-2 Expression and p38MAPK Activity in Cells Infected with Influenza A Virus: IMPACT ON VIRALLY INDUCED APOPTOSIS AND VIRAL REPLICATION. J. Biol. Chem. 284: 16004-16015 [Abstract] [Full Text]  
  • Szretter, K. J., Gangappa, S., Belser, J. A., Zeng, H., Chen, H., Matsuoka, Y., Sambhara, S., Swayne, D. E., Tumpey, T. M., Katz, J. M. (2009). Early Control of H5N1 Influenza Virus Replication by the Type I Interferon Response in Mice. J. Virol. 83: 5825-5834 [Abstract] [Full Text]  
  • Perrone, L. A., Ahmad, A., Veguilla, V., Lu, X., Smith, G., Katz, J. M., Pushko, P., Tumpey, T. M. (2009). Intranasal Vaccination with 1918 Influenza Virus-Like Particles Protects Mice and Ferrets from Lethal 1918 and H5N1 Influenza Virus Challenge. J. Virol. 83: 5726-5734 [Abstract] [Full Text]  
  • Le, Q. M., Sakai-Tagawa, Y., Ozawa, M., Ito, M., Kawaoka, Y. (2009). Selection of H5N1 Influenza Virus PB2 during Replication in Humans. J. Virol. 83: 5278-5281 [Abstract] [Full Text]  
  • Van Hoeven, N., Belser, J. A., Szretter, K. J., Zeng, H., Staeheli, P., Swayne, D. E., Katz, J. M., Tumpey, T. M. (2009). Pathogenesis of 1918 Pandemic and H5N1 Influenza Virus Infections in a Guinea Pig Model: Antiviral Potential of Exogenous Alpha Interferon To Reduce Virus Shedding. J. Virol. 83: 2851-2861 [Abstract] [Full Text]  
  • Katz, J. M., Veguilla, V., Belser, J. A., Maines, T. R., Van Hoeven, N., Pappas, C., Hancock, K., Tumpey, T. M. (2009). The public health impact of avian influenza viruses. Poult. Sci. 88: 872-879 [Abstract] [Full Text]  
  • Van Hoeven, N., Pappas, C., Belser, J. A., Maines, T. R., Zeng, H., Garcia-Sastre, A., Sasisekharan, R., Katz, J. M., Tumpey, T. M. (2009). Human HA and polymerase subunit PB2 proteins confer transmission of an avian influenza virus through the air. Proc. Natl. Acad. Sci. USA 106: 3366-3371 [Abstract] [Full Text]  
  • Yen, H.-L., Aldridge, J. R., Boon, A. C. M., Ilyushina, N. A., Salomon, R., Hulse-Post, D. J., Marjuki, H., Franks, J., Boltz, D. A., Bush, D., Lipatov, A. S., Webby, R. J., Rehg, J. E., Webster, R. G. (2009). Changes in H5N1 influenza virus hemagglutinin receptor binding domain affect systemic spread. Proc. Natl. Acad. Sci. USA 106: 286-291 [Abstract] [Full Text]  
  • Droebner, K., Reiling, S. J., Planz, O. (2008). Role of Hypercytokinemia in NF-{kappa}B p50-Deficient Mice after H5N1 Influenza A Virus Infection. J. Virol. 82: 11461-11466 [Abstract] [Full Text]  
  • Belser, J. A., Blixt, O., Chen, L.-M., Pappas, C., Maines, T. R., Van Hoeven, N., Donis, R., Busch, J., McBride, R., Paulson, J. C., Katz, J. M., Tumpey, T. M. (2008). Contemporary North American influenza H7 viruses possess human receptor specificity: Implications for virus transmissibility. Proc. Natl. Acad. Sci. USA 105: 7558-7563 [Abstract] [Full Text]  
  • Korteweg, C., Gu, J. (2008). Pathology, Molecular Biology, and Pathogenesis of Avian Influenza A (H5N1) Infection in Humans. Am. J. Pathol. 172: 1155-1170 [Abstract] [Full Text]  
  • Li, G., Wang, N., Guzman, H., Sbrana, E., Yoshikawa, T., Tseng, C.-t., Tesh, R. B., Xiao, S.-Y. (2008). Dhori Virus (Orthomyxoviridae: Thogotovirus) Infection of Mice Produces a Disease and Cytokine Response Pattern Similar to That of Highly Virulent Influenza A (H5N1) Virus Infection in Humans. Am J Trop Med Hyg 78: 675-680 [Abstract] [Full Text]  
  • Dittmann, J., Stertz, S., Grimm, D., Steel, J., Garcia-Sastre, A., Haller, O., Kochs, G. (2008). Influenza A Virus Strains Differ in Sensitivity to the Antiviral Action of Mx-GTPase. J. Virol. 82: 3624-3631 [Abstract] [Full Text]  
  • Pappas, C., Aguilar, P. V., Basler, C. F., Solorzano, A., Zeng, H., Perrone, L. A., Palese, P., Garcia-Sastre, A., Katz, J. M., Tumpey, T. M. (2008). Single gene reassortants identify a critical role for PB1, HA, and NA in the high virulence of the 1918 pandemic influenza virus. Proc. Natl. Acad. Sci. USA 105: 3064-3069 [Abstract] [Full Text]  
  • Roti, M., Yang, J., Berger, D., Huston, L., James, E. A., Kwok, W. W. (2008). Healthy Human Subjects Have CD4+ T Cells Directed against H5N1 Influenza Virus. J. Immunol. 180: 1758-1768 [Abstract] [Full Text]  
  • Zeng, H., Goldsmith, C., Thawatsupha, P., Chittaganpitch, M., Waicharoen, S., Zaki, S., Tumpey, T. M., Katz, J. M. (2007). Highly Pathogenic Avian Influenza H5N1 Viruses Elicit an Attenuated Type I Interferon Response in Polarized Human Bronchial Epithelial Cells. J. Virol. 81: 12439-12449 [Abstract] [Full Text]  
  • Yen, H.-L., Ilyushina, N. A., Salomon, R., Hoffmann, E., Webster, R. G., Govorkova, E. A. (2007). Neuraminidase Inhibitor-Resistant Recombinant A/Vietnam/1203/04 (H5N1) Influenza Viruses Retain Their Replication Efficiency and Pathogenicity In Vitro and In Vivo. J. Virol. 81: 12418-12426 [Abstract] [Full Text]  
  • Belser, J. A., Lu, X., Maines, T. R., Smith, C., Li, Y., Donis, R. O., Katz, J. M., Tumpey, T. M. (2007). Pathogenesis of Avian Influenza (H7) Virus Infection in Mice and Ferrets: Enhanced Virulence of Eurasian H7N7 Viruses Isolated from Humans. J. Virol. 81: 11139-11147 [Abstract] [Full Text]  
  • Tumpey, T. M., Szretter, K. J., Van Hoeven, N., Katz, J. M., Kochs, G., Haller, O., Garcia-Sastre, A., Staeheli, P. (2007). The Mx1 Gene Protects Mice against the Pandemic 1918 and Highly Lethal Human H5N1 Influenza Viruses. J. Virol. 81: 10818-10821 [Abstract] [Full Text]  
  • van Riel, D., Munster, V. J., de Wit, E., Rimmelzwaan, G. F., Fouchier, R. A.M., Osterhaus, A. D.M.E., Kuiken, T. (2007). Human and Avian Influenza Viruses Target Different Cells in the Lower Respiratory Tract of Humans and Other Mammals. Am. J. Pathol. 171: 1215-1223 [Abstract] [Full Text]  
  • Hulse-Post, D. J., Franks, J., Boyd, K., Salomon, R., Hoffmann, E., Yen, H. L., Webby, R. J., Walker, D., Nguyen, T. D., Webster, R. G. (2007). Molecular Changes in the Polymerase Genes (PA and PB1) Associated with High Pathogenicity of H5N1 Influenza Virus in Mallard Ducks. J. Virol. 81: 8515-8524 [Abstract] [Full Text]  
  • Twu, K. Y., Kuo, R.-L., Marklund, J., Krug, R. M. (2007). The H5N1 Influenza Virus NS Genes Selected after 1998 Enhance Virus Replication in Mammalian Cells. J. Virol. 81: 8112-8121 [Abstract] [Full Text]  
  • Yen, H.-L., Lipatov, A. S., Ilyushina, N. A., Govorkova, E. A., Franks, J., Yilmaz, N., Douglas, A., Hay, A., Krauss, S., Rehg, J. E., Hoffmann, E., Webster, R. G. (2007). Inefficient Transmission of H5N1 Influenza Viruses in a Ferret Contact Model. J. Virol. 81: 6890-6898 [Abstract] [Full Text]  
  • Taubenberger, J. K., Morens, D. M., Fauci, A. S. (2007). The Next Influenza Pandemic: Can It Be Predicted?. JAMA 297: 2025-2027 [Full Text]  
  • Peiris, J. S. M., de Jong, M. D., Guan, Y. (2007). Avian Influenza Virus (H5N1): a Threat to Human Health. Clin. Microbiol. Rev. 20: 243-267 [Abstract] [Full Text]  
  • Govorkova, E. A., Ilyushina, N. A., Boltz, D. A., Douglas, A., Yilmaz, N., Webster, R. G. (2007). Efficacy of Oseltamivir Therapy in Ferrets Inoculated with Different Clades of H5N1 Influenza Virus. Antimicrob. Agents Chemother. 51: 1414-1424 [Abstract] [Full Text]  
  • Szretter, K. J., Gangappa, S., Lu, X., Smith, C., Shieh, W.-J., Zaki, S. R., Sambhara, S., Tumpey, T. M., Katz, J. M. (2007). Role of Host Cytokine Responses in the Pathogenesis of Avian H5N1 Influenza Viruses in Mice. J. Virol. 81: 2736-2744 [Abstract] [Full Text]  
  • Sidwell, R. W., Barnard, D. L., Day, C. W., Smee, D. F., Bailey, K. W., Wong, M.-H., Morrey, J. D., Furuta, Y. (2007). Efficacy of Orally Administered T-705 on Lethal Avian Influenza A (H5N1) Virus Infections in Mice. Antimicrob. Agents Chemother. 51: 845-851 [Abstract] [Full Text]  
  • Shinya, K., Watanabe, S., Ito, T., Kasai, N., Kawaoka, Y. (2007). Adaptation of an H7N7 equine influenza A virus in mice. J. Gen. Virol. 88: 547-553 [Abstract] [Full Text]  
  • Thomas, J. K., Noppenberger, J. (2007). Avian influenza: A review. Am J Health Syst Pharm 64: 149-165 [Abstract] [Full Text]  
  • Li, Z., Jiang, Y., Jiao, P., Wang, A., Zhao, F., Tian, G., Wang, X., Yu, K., Bu, Z., Chen, H. (2006). The NS1 Gene Contributes to the Virulence of H5N1 Avian Influenza Viruses. J. Virol. 80: 11115-11123 [Abstract] [Full Text]  
  • Maines, T. R., Chen, L.-M., Matsuoka, Y., Chen, H., Rowe, T., Ortin, J., Falcon, A., Hien, N. T., Mai, L. Q., Sedyaningsih, E. R., Harun, S., Tumpey, T. M., Donis, R. O., Cox, N. J., Subbarao, K., Katz, J. M. (2006). Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model. Proc. Natl. Acad. Sci. USA 103: 12121-12126 [Abstract] [Full Text]  
  • Ibricevic, A., Pekosz, A., Walter, M. J., Newby, C., Battaile, J. T., Brown, E. G., Holtzman, M. J., Brody, S. L. (2006). Influenza virus receptor specificity and cell tropism in mouse and human airway epithelial cells.. J. Virol. 80: 7469-7480 [Abstract] [Full Text]  
  • Lowen, A. C., Mubareka, S., Tumpey, T. M., Garcia-Sastre, A., Palese, P. (2006). The guinea pig as a transmission model for human influenza viruses. Proc. Natl. Acad. Sci. USA 103: 9988-9992 [Abstract] [Full Text]  
  • Chen, H., Li, Y., Li, Z., Shi, J., Shinya, K., Deng, G., Qi, Q., Tian, G., Fan, S., Zhao, H., Sun, Y., Kawaoka, Y. (2006). Properties and Dissemination of H5N1 Viruses Isolated during an Influenza Outbreak in Migratory Waterfowl in Western China.. J. Virol. 80: 5976-5983 [Abstract] [Full Text]  
  • Stephenson, I., Democratis, J. (2006). Influenza: current threat from avian influenza. Br Med Bull 75-76: 63-80 [Abstract] [Full Text]  
  • Stevens, J., Blixt, O., Tumpey, T. M., Taubenberger, J. K., Paulson, J. C., Wilson, I. A. (2006). Structure and Receptor Specificity of the Hemagglutinin from an H5N1 Influenza Virus. Science 312: 404-410 [Abstract] [Full Text]  
  • van Riel, D., Munster, V. J., de Wit, E., Rimmelzwaan, G. F., Fouchier, R. A. M., Osterhaus, A. D. M. E., Kuiken, T. (2006). H5N1 Virus Attachment to Lower Respiratory Tract. Science 312: 399-399 [Abstract] [Full Text]  
  • Salomon, R., Franks, J., Govorkova, E. A., Ilyushina, N. A., Yen, H.-L., Hulse-Post, D. J., Humberd, J., Trichet, M., Rehg, J. E., Webby, R. J., Webster, R. G., Hoffmann, E. (2006). The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04. JEM 203: 689-697 [Abstract] [Full Text]  
  • Wong, S. S. Y., Yuen, K.-y. (2006). Avian Influenza Virus Infections in Humans. Chest 129: 156-168 [Abstract] [Full Text]  
  • de Jong, M. D., Thanh, T. T., Khanh, T. H., Hien, V. M., Smith, G. J.D., Chau, N. V., Cam, B. V., Qui, P. T., Ha, D. Q., Guan, Y., Peiris, J.S. M., Hien, T. T., Farrar, J. (2005). Oseltamivir Resistance during Treatment of Influenza A (H5N1) Infection. NEJM 353: 2667-2672 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»