Molecular basis of enterovirus 71 neuropathogenicity

2014 Fiscal Year Final Research Report

• Project/Area Number: 23390116
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: KOIKE Satoshi 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 副参事研究員 (30195630)
• Co-Investigator(Kenkyū-buntansha): FUJII Ken 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 主任研究員 (10580201) ; YAMAYOSHI Seiya 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (50529534)
• Co-Investigator(Renkei-kenkyūsha): NAGATA Noriyo 国立感染症研究所, 感染病理部, 室長 (30270648) ; SHIMIZU Hiroyuki 国立感染症研究所, ウイルス第二部, 室長 (90270644)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: エンテロウイルス７１ / 神経病原性 / マウス感染モデル

Outline of Final Research Achievements

The host range of enterovirus 71 (EV71) is restricted to primates with some exceptions. Therefore it was difficult to evalate the neurovirulence level of EV71 strains. We have established a transgenic mouse model that expressed a cellular receptor for EV71, human Scavenger receptor B2 (SCARB2). The transgenic mice became susceptible to EV71. They showed efficient EV71 replication in neurons in the CNS and neurological signs similar to those observed in human severe cases infected with EV71.
We inoculated several EV71 strains and compared the virulence of these strains. The inoculated virus exhibited different virulence levels, suggesting that the tg mice are useful model. We then evaluated the effect of a single amino acid substitution Gly to Glu at position 145 of the VP1 capsid protein. The virus with Glu at this position significantly increased the virulence compared to that with Gly. The result suggested that this amino acid is an important virulence determinant in EV71.

Free Research Field

ウイルス学