The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
A new influenza virus virulence determinant: The NS1 protein four C-terminal residues modulate pathogenicity
Open accessAbstract
The virulence of influenza virus is a multigenic trait. One determinant of virulence is the multifunctional NS1 protein that functions in several ways to defeat the cellular innate immune response. Recent large-scale genome sequence analysis of avian influenza virus isolates indicated that four C-terminal residues of the NS1 protein is a PDZ ligand domain of the X-S/T-X-V type and it was speculated that it may represent a virulence determinant. To test this hypothesis, by using mice as a model system, the four C-terminal amino acid residues of a number of influenza virus strains were engineered into the A/WSN/33 virus NS1 protein by reverse genetics and the pathogenicity of the viruses determined. Viruses containing NS1 sequences from the 1918 H1N1 and H5N1 highly pathogenic avian influenza (HPAI) viruses demonstrated increased virulence in infected mice compared with wt A/WSN/33 virus, as characterized by rapid loss of body weight, decreased survival time, and decreased mean lethal dose. Histopathological analysis of infected mouse lung tissues demonstrated severe alveolitis, hemorrhaging, and spread of the virus throughout the entire lung. The increase in pathogenicity was not caused by the overproduction of IFN, suggesting the NS1 protein C terminus may interact with PDZ-binding protein(s) and modulate pathogenicity through alternative mechanisms.
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1 retracted
RETRACTED: The NS1 gene of H5N1 influenza viruses circumvents the host anti-viral cytokine responses
Seo, S. H., Hoffmann, E., & Webster, R. G. (2004) · Virus Research · doi:10.1016/j.virusres.2004.02.022 · Cited by 145
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Self-citationPDZ Domains and the Organization of Supramolecular Complexes
Sheng, M., & Sala, C. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1 · Cited by 1,200
Rescue of Influenza A Virus from Recombinant DNA
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Activation of Interferon Regulatory Factor 3 Is Inhibited by the Influenza A Virus NS1 Protein
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Cited by
The multifunctional NS1 protein of influenza A viruses
Hale, B. G., Randall, R. E., Ortín, J., & Jackson, D. (2008) · Journal of General Virology · doi:10.1099/vir.0.2008/004606-0 · Cited by 1,079
Self-citationInfluenza A viruses: new research developments
Medina, R. A., & García-Sastre, A. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2613 · Cited by 677
Suppression of the antiviral response by an influenza histone mimic
Marazzi, I., Ho, J. S. Y., Kim, J., Manicassamy, B., Dewell, S., Albrecht, R. A., Seibert, C. W., Schaefer, U., Jeffrey, K. L., Prinjha, R. K., et al. (2012) · Nature · doi:10.1038/nature10892 · Cited by 310
Innate immune responses to influenza A H5N1: friend or foe?
Peiris, J. S. M., Cheung, C. Y., Leung, C. Y. H., & Nicholls, J. M. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.09.004 · Cited by 232
Emerging theme: cellular PDZ proteins as common targets of pathogenic viruses
Javier, R. T., & Rice, A. P. (2011) · Journal of Virology · doi:10.1128/jvi.05410-11 · Cited by 198
Metadata
- Authors
- Jackson, D., Hossain, M. J., Hickman, D., Perez, D. R., & Lamb, R. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2008-03-18
- Volume
- 105
- Issue
- 11
- Pages
- 4381-4386
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2106599854
- Cited by
- 403
- References
- 38
- FWCI
- 29.12
- Type
- journal article
- Language
- en
- Open access
- green
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- Jackson, D., Hossain, M. J., Hickman, D., Perez, D. R., & Lamb, R. A. (2008). A new influenza virus virulence determinant: The NS1 protein four C-terminal residues modulate pathogenicity. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0800482105
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