The research group led by Professor Satoshi Kawamoto of Fujita Medical University succeeded in artificial synthesis of human rotavirus for the first time in the world through joint research with Researcher Chitose Koyama of Kitasato University.This is expected to elucidate the pathogenicity expression mechanism and accelerate the development of next-generation vaccines and therapeutic agents that are highly safe for humans.
Rotavirus, which causes severe diarrhea in infants, has been eagerly awaited for the construction of "reverse genetics," which is a technology for artificially synthesizing infectious viruses in order to develop safe vaccines and therapeutic agents.However, since rotavirus has as many as 11 gene fragments inside, it was necessary to introduce all 11 artificially synthesized genes into one cell at the same time, which was difficult to construct. The first reverse genetics were developed in 2017 using salrotavirus, but this system failed with human rotavirus.
研究グループは2018年に、動物ロタウイルスの11本の遺伝子のうち、2種類の遺伝子(非構造タンパク質NSP2とNSP5)を他の9本の遺伝子の3倍量にして細胞に導入することで、従来の約1,000倍効率良く、ロタウイルスを人工合成できることを見出した。そこで今回、ヒトロタウイルスの11本の遺伝子のうち、NSP2とNSP5遺伝子を他の9本の遺伝子の3倍量にし、さらにロタウイルス胃腸炎患者便中のウイルスを効率良く分離する技術(高濃度のトリプシン添加と回転培養)を利用することで、ヒトロタウイルスの人工合成に成功した。
With this achievement, the human rotavirus gene can be freely modified, and the mechanism of natural human rotavirus infection, proliferation, and pathogenicity can be reproduced, so that a next-generation rotavirus vaccine with excellent human safety is possible. It is expected that the development of rotavirus and therapeutic agents will progress dramatically.
Paper information:[Journal of Virology] Generation of infectious recombinant human rotaviruses from just 11 cloned cDNAs encoding the rotavirus genome