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Dengue Virus

Nonstructural Protein (NS)1 and Pathogenesis

  • Dengue virus (DENV) NS1 protein (soluble form NS1, sNS1) circulates in patient's blood without incorporation into virus particle. Patients produce anti-NS1 antibodies (Abs). The sNS1 and/or anti-NS1 Abs in patients is thought to be involved in pathogenesis of dengue hemorrhagic fever.
  • We study the role of NS1 and anti-NS1 Abs in patients to understand their possible involvement in pathogenesis. In addition, we study any function of NS1 in virus replication.

Development of Animal Models Using Mice for Dengue Pathogenesis

  • Dengue hemorrhagic fever is due to the plasma leakage. It is believed that such severe dengue illness is caused by host immune responses but not by dengue virus itself. The mechanism of plasma leakage remains unknown.
  • To understand the mechanism of dengue pathogenesis as well as to develop the therapeutics and vaccine, it is necessary to develop animal model for dengue illness. We are trying to develop animal model using knockout mice and recombinant viruses.

Preparation of Human Monoclonal Antibodies and Its Application

  • In order to develop the therapeutic monoclonal antibody and to understand dengue pathogenesis, we examine the neutralizing activity and antibody-dependent enhancement (ADE) of individual monoclonal antibodies that were prepared by use of peripheral blood lymphocytes from patients with dengue illness. ADE phenomena is the hypothesis to explain for the patients' condition to exaggerate by enhancing viral replication.

  • We have succeeded to obtain human monoclonal antibodies. Currently, we characterize these antibodies for their functions of viral neutralization and ADE to individual dengue virus belonging to four serotypes.

Quasispecies of Dengue Virus

  • Dengue virus transmits between human and mosquito as a various virus population, so-called quasispecies, which are diverse virus population, consisting of many mutant viruses derived from one or few strains of virus. Most of RNA viruses including dengue virus exist as quasispecies because their RNA polymerases lack proofreading activity.

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