Laboratories

Laboratory of Infectious Control Science Recruiting students for the academic year 2018

Professor Chieko KAI
+81-3-5449-5497
E-mail: ckai{at}ims.u-tokyo.ac.jp
Lab HP

Associate Professor Misako YONEDA
+81-3-5449-5498
E-mail: yone{at}ims.u-tokyo.ac.jp

Introduction

【Keywords】Virology, Emerging viruses, Development of vaccine, Animal experiments, Cancer therapy.

 Emerging infectious diseases pose a serious threat to human and animal health. It is believed that cross-species transmission is the most common way for a virus to acquire a new host species. Therefore, clarification of mechanisms underlying cross-species transmission is the fundamental subjects in virology. However, it remains still unsolved. To reveal mechanism of cross-species virus transmission and pathogenicity in its host animal species, we are studying virus-host interactions of Mononegavirales in vitro and in vivo, a group of RNA virus possessing a single stranded RNA genome, that contains many highly pathogenic emerging viruses.
 We have first established reverse genetics systems of Mononegavirales (measles virus, rinderpest virus, canine distemper virus, and Nipah virus), by which infectious recombinant viruses can be generated from fulllength cDNA clone of the viruses. By using reverse genetics techniques with our excellent animal infection models of the viruses, we have searched viral genes responsible for cross-species transmission and pathogenicity. We are also studying host factors associating with the viruses for a comprehensive understanding of virus-host interactions. Our findings are expected to contribute for understanding of molecular mechanisms of diseases caused by virus infection such as immunosuppression, neuropathogenicity and persistent infection, which could lead to development of novel therapies for virus infectious diseases.


Fig. 1. Development of bivalent leishmaniasis vaccine by reverse genetics system.


 Morbilliviruses are possible to apply as an excellent vaccine vector because of its lifelong immunity and strong induction of cellular immunity after infection. We, therefore, have generated polyvalent vaccines for leishmaniasis or Nipah virus infection, there were no vaccines for these diseases, and verified its effectiveness by in vivo experiments. We have actively applied our new recombinant virus technique to develop polyvalent vaccines.
 Measles virus is able to infect and kill cancer cells. We have successfully produced a recombinant attenuated measles virus which maintains the infectivity and lethality to cancer cells by using reverse genetics technique. Additionally, we have demonstrated that this recombinant virus is effective for various types of cancer in the experiments of xenografted mice. We have also investigated the effective dose and route of administration and molecular level evidence of the recombinant virus treatment. Currently, we are utilizing this recombinant virus to develop a new cancer therapy and heading to translational research.

Fig. 2. Localization of the recombinant measles virus in xenografted mice.

 Nipah virus that emerged in 1999 from fruit bats as its natural host is a highly virulent virus in humans with a high mortality rate and is classified into biosafety level 4 (BSL4). It still breaks out in Asia every year, but there are currently no vaccines and treatment licensed for human use. Development of vaccines and antiviral drugs for virus infectious diseases is one of our goals.

Laboratories

The University of Tokyo
Graduate School of Frontier Sciences, The University of Tokyo

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