Host-pathogen interactions of influenza virus
Influenza is one of the most important respiratory infectious diseases of humans. It is estimated that influenza is responsible for 250,000 to 500,000 deaths annually. Genome sequences of currently circulating virus isolates are important sources of information about influenza. Significant efforts have been made to build public resources of influenza viruses such as the Influenza Virus Resource (http://www.ncbi.nlm.nih.gov/genomes/FLU/FLU.html) at the National Center for Biotechnology Information (NCBI), the Influenza Sequence Database at Los Alamos National Laboratory, the Influenza Virus Database (http://influenza.genomics.org.cn) at the Beijing Institute of Genomics, and the BioHealthBase Bioinformatics Resource Center (http://www.biohealthbase.org) (1-4). An increasing number of genomes of influenza viruses have been sequenced in Asia in recent years. Southern China has long been considered a potential epicenter for emergence of pandemic influenza viruses and becomes one of the major foci for viral surveillance.
Recent develoments :
In order to leverage the wealth of information, we have developed an integrated user friendly relational database, Influenza Sequence and Epitope Database (ISED) (1), particularly focusing on the genomes of the seasonal influenza viruses from Asian countries. We have added value by implementing a suite of bioinformatics tools that can be used to analyze and visualize the influenza data. This freely accessible resource will augment influenza research and contribute to improved public heath.
We wish to acknowledge the technical support from Mr. C. H. Gong at the department of Biotechnology and Bioinformatics and Mr. J. H. Yeom of the E-Front, Seoul, Korea. This work was supported by the Korea National Institute of Health and a grant from the BioGreen 21 Program and the Basic Research Program of the Korea Science and Engineering Foundation.
1. Bao, Y., Bolotov, P., Dernovoy, D., Kiryutin, B., Zaslavsky, L., Tatusova, T., Ostell, J., and Lipman, D. (2008) The influenza virus resource at the national center for biotechnology information. J. Virol. 82, 596-601.
2. Macken, C., Lu, H., Goodman, J. and Boykin, L. (2001) In Osterhaus, A.D.M.E., Cox, N., and Hampson, A.W. (eds) Options for the control of influenza IV. Elsevier Science, Amsterdam, pp. 103-106.
3. Chang, S., Zhang, J., Liao, X., Zhu, X., Wang, D., Zhu, J., Feng, T., Zhu, B., Gao, G.F., Wang, J. et al. (2007) Influenza virus database (IVDB): an integrated information resource and analysis platform for influenza virus research. Nucl. Acids Res. 35, D376-D380.
4. Squires, B., Macken, C., Garcia-Sastre, A., Godbole, S., Noronha, J., Hunt, V., Chang, R., Larsen, C.N., Klem, E., Biersack, K. et al. (2008) BioHealthBase: informatics support in the elucidation of influenza virus host-pathogen interactions and virulence. Nucl. Acids Res. 36, D497-D503.
The NCBI Influenza Virus Sequence Database (http://www.ncbi.nlm.nih.gov/genomes/FLU/FLU.html) contains nucleotide sequences, protein sequences and their encoding regions of all influenza viruses in GenBank. The database is updated usually within a day or two after new sequences become available in GenBank. Information for database fields (subtype, segment, host, country, year etc.) are extracted automatically from GenBank records, and examined by NCBI staff. Information not available in GenBank records are obtained from literature or direct contact with sequence submitters, whenever possible. There are 4 major applications of the NCBI Influenza Virus Sequence Database: database browsing and sequence retrieving; complete genome sets finding; multiple sequence alignment; and cluster or phylogenetic tree building. All of these applications start from the database query page with slightly different restrictions for certain applications (e.g. sequences from different segments cannot be mixed for multiple sequence alignment or tree building). For users convenience, individual interfaces were custom-made for each application. Data in the NCBI Influenza Virus Sequence Database are available for downloading from ftp://ftp.ncbi.nih.gov/genomes/INFLUENZA/. <ftp://ftp.ncbi.nih.gov/genomes/INFLUENZA/.
1. Ghedin E, Sengamalay NA, Shumway M, Zaborsky J, Feldblyum T, Subbu V, Spiro DJ, Sitz J, Koo H, Bolotov P, Dernovoy D, Tatusova T, Bao Y, St George K, Taylor J, Lipman DJ, Fraser CM, Taubenberger JK, Salzberg SL. (2005) Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution. Nature 437: 1162-1166.
Frequent outbreaks of highly pathogenic avian influenza and the increasing data available for comparative analysis require a central database specialized in influenza viruses. We have established the Influenza Virus Database (IVDB) to integrate information and create an analysis platform for genetic, genomic, and phylogenetic studies of the virus. IVDB hosts complete genome sequences of influenza A virus generated by Beijing Institute of Genomics and curates all other published influenza virus sequences after expert annotation. Our Q-Filter system classifies and ranks all nucleotide sequences into 7 categories according to sequence content and integrity. IVDB provides a series of tools and viewers for comparative analysis of the viral genomes, genes, genetic polymorphisms and phylogenetic relationships. A search system has been developed for users to retrieve a combination of different data types by setting search options. To facilitate analysis of global viral transmission and evolution, the IV Sequence Distribution Tool (IVDT) has been developed to display the worldwide geographic distribution of chosen viral genotypes and to couple genomic data with epidemiological data. The BLAST, multiple sequence alignment and phylogenetic analysis tools were integrated for online data analysis. Furthermore, IVDB offers instant access to pre-computed alignments and polymorphisms of influenza virus genes and proteins, and presents the results as SNP distribution plots and minor allele distributions.
The work was sponsored by an institutional grant from the Beijing Institute of Genomics, Chinese Academy of Sciences. GFG is supported by National Basic Research Program 973 (Grant No. 2005CB523001) from Ministry of Science and Technology, China. We are indebted to all our collaborators, IV sample providers and other IV sequence producers for their contribution and kind support to the IVDB database. Funding to pay the Open Access publication charges for this article was provided by an institutional grant from the Beijing Institute of Genomics, CAS.
Influenza Virus Resource presents data obtained from the NIAID Influenza Genome Sequencing Project as well as from GenBank, combined with tools for flu sequence analysis and annotation. In addition, it provides links to other resources that contain flu sequences, publications and general information about flu viruses.