Understanding the Replication Cycle of Influenza Virus and Its Application

Yoshihiro Kawaoka (Professor, The University of Tokyo)

Research area: Translational Research for Intractable Immune Disorders and Infectious Diseases(2001-2006) CREST
ERATO(2008-2013) ERATO
Development of virus synthesis technique
Facilitating the manufacture of the new influenza vaccine that has proved so difficult

Research Overview
Seasonal influenza viruses threaten the lives of older people and children. The aim of this research is to overcome viral infection by understanding the relationships between viral genes and those of the host to enable the development of antiviral drugs and live vaccines. The original method for artificial synthesis of viruses was used to (1) elucidate the replication mechanism of influenza virus, (2) determine the molecular basis for virulence of highly pathogenic viruses such as Spanish influenza virus, and (3) develop new vaccines.

Impact of Research Achievements
■ Information that contributes to the formulation of countermeasures for and control of pandemics was provided by identifying the pathogenicity mechanism of viruses such as highly pathogenic H5N1 avian influenza, Spanish flu and Ebola hemorrhagic fever.
■ A virus synthesis technique (reverse genetics) was applied to vaccine development, which was difficult with conventional techniques.
- An attenuated recombinant virus was prepared to develop a vaccine against H5N1 avian influenza virus.
- A chimeric virus was prepared to develop an influenza B virus vaccine without interference with influenza A virus.
- Recombinant viruses were used to develop a multivalent vaccine that is effective against multiple viral infections.
■ Technology to allow easy development of a vaccine against highly-virulent viruses that has proved so difficult to manufacture.
Number of fatalities: Tens of millions (Spanish flu [highly virulent]), minimum 16 thousand. (Swine flu [attenuated] As of March 2010)

 Inner structure of budding A virus particles (cross sections)  Artificial synthesis of influenza virus (schematic diagram)