Kobayashi Lab／Research Center for Infectious Disease Control  Department of Virology

Members of the family Reoviridae possess 9–12 segmented double-stranded RNA genomes. This family includes important pathogens, including the rotaviruses, in humans and animals. In our laboratory, using original technology to generate recombinant Reoviridae viruses from cloned cDNAs, we are studying molecular mechanisms underlying Reoviridae virus replication and pathogenesis, and developing novel vaccine vectors. More recently, we have also succeeded in developing a unique reverse genetics system using small fish for norovirus, which, like rotavirus, causes diarrheal disease. We are further extending this genetic manipulation approach to basic research on other diarrheal viruses, including norovirus.

1) Rotavirus

Rotaviruses (RVs) are highly important pathogens that cause severe diarrhea in infants and young children worldwide. Understanding of the molecular mechanisms underlying the replication and pathogenesis of RVs has been hampered by the lack of a reverse genetics system that allows the synthesis of recombinant viruses from artificial genes. In 2017, we developed a plasmid-based reverse genetics system for RVs. We are investigating RV biology and developing vaccines and therapeutics using a combination of genetic, biochemical, and biophysical approaches.

2) Norovirus

Noroviruses are highly important pathogens that cause acute gastroenteritis worldwide. Understanding of the molecular mechanisms underlying the replication and pathogenesis of noroviruses has been hampered by the lack of robust culture and genetic manipulation systems. Recently, we developed a long-awaited reverse genetics system for noroviruses. We are investigating norovirus biology and developing preventive and therapeutic strategies using this technology.

3) Oncolytic viral therapy using reovirus

Mammalian orthoreoviruses (reoviruses) are highly tractable experimental models for studying the replication and pathogenesis of dsRNA viruses. Reoviruses have been evaluated as oncolytic agents against a variety of tumors, including head and neck, colon, breast, and pancreatic cancers, in animal models and humans. Wild-type reovirus-based oncolytic therapies are safe, but their efficacy is currently limited. We are developing safer and more effective reovirus-based cancer therapeutics by genetic modification.

4) Highly pathogenic bat-borne reovirus

Nelson Bay reovirus (NBV) was isolated from a flying fox in 1968 but had not been associated with any disease. However, NBVs were recently isolated from human patients suffering from acute respiratory tract infections in Malaysia, Indonesia, China, and Japan. These isolates have given rise to increasing concerns about bat-transmitted reovirus infections in humans. We are investigating how NBV replicates and causes disease in vitro and in vivo.