International Research Center for Infectious Diseases

Laboratory of Viral Infection

Research Group / Research Projects / Major publications /

Research Group

Research Projects

◆ Molecular mechanism of H5N1 avian influenza virus pathogenesis
In recent years, the highly pathogenic avian influenza virus (AIV) H5N1 emerged from southeast Asia and raised serious worldwide concern about the risk of an influenza pandemic. However, how H5N1 induces disease remains poorly understood. We are using in vitro and animal experiments to study the role the viral glycoprotein hemagglutinin (HA) plays in viral growth and cell toxicity. Recent achievements are listed below:By genetically changing H5 AIV by recombinant DNA techniques, H5N1-HA has been shown to be one of the major viral factors that determine lethality in mice. We confirmed that the pathogenicity of HA depends on its cleavage sequence, which is consistent with previous observations. However, our further experiments suggest that other region(s) and amino acids of H5N1-HA may also participate in the pathogenicity of H5N1.
That H5N1-HA can induce significant cellular toxicity was demonstrated by in vitro experiments. We showed that H5N1-HA-specific cell toxicity (apoptosis) was observed in porcine as well as human primary airway epithelial cells. Similar results were also observed in primary cells from a water fowl known to be a natural AIV host. In contrast, HA proteins from previously isolated AIVs, including the H5 subtype, did not induce this severe cell toxicity. Thus, the genotype of HA may be critical for the pathogenicity and/or cellular toxicity of H5N1 AIVs.

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◆ Metagenomic analysis of viral pathogens in humans: Development of Pathogen Identification System by using a high-throughput "Next-Generation" DNA sequencer (RAPID system; Department of Infection Metagenomics)
We are establishing a protocol to rapidly obtain the whole genome information of viral pathogens. This is expected to significantly accelerate the speed with which pathogens can be identified. Using this protocol, we have successfully demonstrated the presence of pathogenic microbes in clinical human samples without resorting to conventional selective procedures for specific pathogens.


Major publications

  1. Daidoji T, Kaihatsu K, Nakaya T. The role of apoptosis in influenza virus pathogenesis and the mechanisms involved in anti-influenza therapies. Curr Chem Biol [Review, in press]
  2. Ueda M, Daidoji T, Du A, Yang CS, Ibrahim MS, Ikuta K, Nakaya T. Highly pathogenic H5N1 avian influenza virus induces extracellular Ca2+ influx, leading to apoptosis in avian cells. J Virol. 2010 84(6):3068-78.
  3. Nakamura S, Yang CS, Sakon N, Ueda M, Tougan T, Yamashita A, Goto N, Takahashi K, Yasunaga T, Ikuta K, Mizutani T, Okamoto Y, Tagami M, Morita R, Maeda N, Kawai J, Hayashizaki Y, Nagai Y, Horii T, Iida T, Nakaya T. Direct metagenomic detection of viral pathogens in nasal and fecal specimens using an unbiased high-throughput sequencing approach. PLoS ONE. 2009 4(1):e4219.
  4. Du A, Daidoji T, Koma T, Ibrahim MS, Nakamura S, de Silva UC, Ueda M, Yang CS, Yasunaga T, Ikuta K, Nakaya T. Detection of circulating Asian H5N1 viruses by a newly established monoclonal antibody. Biochem Biophys Res Commun. 2009 378(2):197-202.
  5. Daidoji T, Koma T, Du A, Yang CS, Ueda M, Ikuta K, Nakaya T. H5N1 avian influenza virus induces apoptotic cell death in mammalian airway epithelial cells. J Virol. 2008 82(22): 11294-307.
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