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Large Scale Sequence Analysis of Avian Influenza Isolates

John C. Obenauer, Jackie Denson, Perdeep K. Mehta, Xiaoping Su, Suraj Mukatira, David B. Finkelstein, Xiequn Xu, Jinhua Wang, Jing Ma, Yiping Fan, Karen M. Rakestraw, Robert G. Webster, Erich Hoffman, Scott Krauss, Jie Zheng, Ziwei Zhang, and Clayton W. Naeve*.

* To whom correspondence should be addressed. Email: clayton.naeve@stjude.org

Science 2006 Mar 17;311(5767):1576-80.

Summary

The first large scale sequencing of avian influenza viruses doubles the amount of genetic data on these key pathogens and reveals a potential virulence determinant.

Abstract

The spread of H5N1 avian influenza viruses (AIV) from China to Europe has raised significant global concern about their potential to infect humans and cause a pandemic. In spite of their significant threat to human health, remarkably little AIV whole genome information is available. We report here a preliminary analysis of the first large scale sequencing of AIV including 2,196 AIV genes and 169 complete genomes. We combine this new information with public AIV data to identify new gene alleles, persistent genotypes, compensatory mutations, and a potential virulence determinant.

Tables 1-3
  Table 1. Project Summary. All 11 transcripts from the 8 gene segments of AIV are listed along with their lengths in nucleotides (nt), the number of complete gene sequences produced in this study, and the total number of finished nucleotides by segment.
[ Open | Download Excel Version ]
  Table 2. Distribution of PDZ ligand domains (PL) in 1,196 influenza NS proteins.
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  Table 3. PDZ binding studies.
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Figures 1-3
  Figure 1. Proteotype assignment for the NS gene/protein.
[ Open ] [ PDF 1.63MB | PNG 30KB ]
  Figure 2. Proteotyping complete genomes.
[ Open ] [ PDF 2.32MB | PNG 238KB ]
  Figure 3. PDZ domain array analysis.
[ Open ] [ PDF 1.27MB | PNG 735KB ]
   
Tables S1-S6
  Table S1. Viruses included in study.
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  Table S2. Public AIV sequences used in study.
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  Table S3. Human proteins determined to bind avian NS1 protein.
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  Table S4. Public NS sequences used in PL distribution analysis.
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  Table S5. Primers used for amplification and sequencing.
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  Table S6. Supplementary Information. Parameter values of each segment for MCMC phylogenetic analysis.
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Figure S1-S15
  Figure S1. Phylogenetic analysis of 4,339 AIV genes.
[ Open ] [ PDF 1.49MB | PNG 258KB ]
  Figure S2. Proteogram for 622 NS sequences (82.5% conservation).
[ Open ] [ PDF 1.92MB | PNG 227KB ]
  Figure S3. Proteogram for 745 M sequences (97.4% conservation).
[ Open ] [ PDF 6.30MB | PNG 364KB ]
  Figure S4. Proteogram for 531 NA sequences (58.2% conservation).
[ Open ] [ PDF 6.44MB | PNG 371KB ]
  Figure S5. Proteogram for 519 NP sequences (98.7% conservation).
[ Open ] [ PDF 3.64MB | PNG 207KB ]
  Figure S6. Proteogram for 692 HA sequences (57.7% conservation).
[ Open ] [ PDF 6.25MB | PNG 827KB ]
  Figure S7. Proteogram for 418 PA sequences (99.0% conservation).
[ Open ] [ PDF 860KB |PNG 192KB ]
  Figure S8. Proteogram for 395 PB2 sequences (98.1% conservation).
[ Open ] [ PDF 691KB | PNG 158KB ]
  Figure S9. Proteogram for 396 PB1 sequences (99.3% conservation).
[ Open ] [ PDF 868KB | PNG 248KB ]
  Figure S10. Proteotyping 169 complete AIV genomes.
[ Open ] [ PDF 1.28MB | PNG 266KB ]
  Figure S11. Testing binding of peptide GSESEV to PDZ domains by NMR.
[ Open ] [ PDF 3.49MB | PNG 880KB ]
  Figure S12. Testing binding of peptide GSEPEV to PDZ domains by NMR.
[ Open ] [ PDF 2.53MB | PNG 650KB ]
  Figure S13. Testing binding of peptide GSKSEV to PDZ domains by NMR.
[ Open ] [ PDF 3.59MB | PNG 830KB ]
  Figure S14. Testing binding of peptide GSRSKV to PDZ domains by NMR.
[ Open ] [ PDF 3.21MB | PNG 858KB ]
  Figure S15. Analysis of concatenated genomes.
[ Open ] [ PDF 2.78MB | PNG 530KB ]