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Journal of Virology, May 2008, p. 4544-4553, Vol. 82, No. 9
0022-538X/08/$08.00+0     doi:10.1128/JVI.02642-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

NP, PB1, and PB2 Viral Genes Contribute to Altered Replication of H5N1 Avian Influenza Viruses in Chickens{triangledown} ,{ddagger}

Jamie L. Wasilenko,1 Chang Won Lee,2,3,{dagger} Luciana Sarmento,1 Erica Spackman,1 Darrell R. Kapczynski,1 David L. Suarez,1 and Mary J. Pantin-Jackwood1*

Southeast Poultry Research Laboratory, USDA-Agricultural Research Service, Athens, Georgia,1 Department of Food Animal Health Research Program, OARDC, The Ohio State University, Wooster, Ohio,2 Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio3

Received 12 December 2007/ Accepted 15 February 2008

The virulence determinants for highly pathogenic avian influenza viruses (AIVs) are considered multigenic, although the best characterized virulence factor is the hemagglutinin (HA) cleavage site. The capability of influenza viruses to reassort gene segments is one potential way for new viruses to emerge with different virulence characteristics. To evaluate the role of other gene segments in virulence, we used reverse genetics to generate two H5N1 recombinant viruses with differing pathogenicity in chickens. Single-gene reassortants were used to determine which viral genes contribute to the altered virulence. Exchange of the PB1, PB2, and NP genes impacted replication of the reassortant viruses while also affecting the expression of specific host genes. Disruption of the parental virus' functional polymerase complexes by exchanging PB1 or PB2 genes decreased viral replication in tissues and consequently the pathogenicity of the viruses. In contrast, exchanging the NP gene greatly increased viral replication and expanded tissue tropism, thus resulting in decreased mean death times. Infection with the NP reassortant virus also resulted in the upregulation of gamma interferon and inducible nitric oxide synthase gene expression. In addition to the impact of PB1, PB2, and NP on viral replication, the HA, NS, and M genes also contributed to the pathogenesis of the reassortant viruses. While the pathogenesis of AIVs in chickens is clearly dependent on the interaction of multiple gene products, we have shown that single-gene reassortment events are sufficient to alter the virulence of AIVs in chickens.

* Corresponding author. Mailing address: Southeast Poultry Research Laboratory, USDA-ARS, 934 College Station Road, Athens, GA 30605. Phone: (706) 546-3419. Fax: (706) 546-3161. E-mail: Mary.Pantin-Jackwood{at}ARS.USDA.gov

{triangledown} Published ahead of print on 27 February 2008.

{ddagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{dagger} Present address: Department of Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Avenue, Wooster, OH 44691-4096.

Journal of Virology, May 2008, p. 4544-4553, Vol. 82, No. 9
0022-538X/08/$08.00+0     doi:10.1128/JVI.02642-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • 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]  
  • Hoper, D., Hoffmann, B., Beer, M. (2009). Simple, Sensitive, and Swift Sequencing of Complete H5N1 Avian Influenza Virus Genomes. J. Clin. Microbiol. 47: 674-679 [Abstract] [Full Text]  


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