Molecular Determinant Of Canine Distemper Virus To Modulate Usage Of The Human Receptors

• Project/Area Number: 25850202
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Veterinary medical science
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: SAKAI KOUJI 国立感染症研究所, その他部局等, 主任研究官 (70515535)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: CDV / SLAM / nectin4 / ヒト / 宿主域 / 受容体 / イヌジステンパーウイルス / ウイルス / レセプター / 変異 / 感染症 / 獣医学 / 人獣共通感染症 / 実験動物学

Outline of Final Research Achievements

A canine distemper virus (CDV) strain, CYN07-dV, associated with a lethal outbreak in monkeys, used human signaling lymphocyte activation molecule as a receptor only poorly but readily adapted to use it following a R519S, D540G or P541S substitution in the hemagglutinin protein. Since CYN07-dV had an intrinsic ability to use human nectin-4, the adapted virus became able to use both human immune and epithelial cell receptors, as well as monkey and canine ones, suggesting that CDV can potentially infect humans.　Unlike the CYN07-dV strain, these mutations did not confer hSLAM-using ability on the H proteins of wild-type CDV isolates. Our data demonstrated that a unique mutation of the CYN07-dV strain to adapt to humans and that the additional unique mutation in the H protein of wild-type CDV isolates is required to confer hSLAM-using ability.

Research Products

• [Journal Article] Canine distemper virus associated with a lethal outbreak in monkeys can readily adapt to use human receptors. (2013)
  • Author(s): Sakai K, Yoshikawa T, Seki F, Fukushi S, Tahara M, Nagata N, Ami Y, Mizutani T, Kurane I, Yamaguchi R, Hasegawa H, Saijo M, Komase K, Morikawa S, Takeda M.
  • Journal Title: J Virol Volume: 87 Issue: 12 Pages: 7170-7175
  • DOI: 10.1128/jvi.03479-12
  • Peer Reviewed
• [Presentation] Host range and cell tropism determinants of measles virus and canine distemper virus (2014)
  • Author(s): Makoto Takeda, Kouji Sakai, Fumio Seki, and Noriyuki Otsuki
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: 横浜、日本
  • Year and Date: 2014-11-10 – 2014-11-13
  • Invited
• [Presentation] 犬ジステンパーウイルスの霊長類レセプター利用に関する解析 (2014)
  • Author(s): 酒井宏治
  • Organizer: Third Negative Strand Virus – Japan Symposium
  • Place of Presentation: 沖縄、日本
• [Presentation] High potential of canine distemper virus in the ability to use macaca and human receptors (2013)
  • Author(s): Kouji SAKAI
  • Organizer: 15th International. Negative Strand Virus Meeting.
  • Place of Presentation: Granada, Spain
• [Presentation] サルから分離された犬ジステンパーウイルスのヒト受容体利用能獲得に必要な変異 (2013)
  • Author(s): 酒井宏治
  • Organizer: 第156回日本獣医学会学術集会
  • Place of Presentation: 岐阜、日本
• [Presentation] 犬ジステンパーウイルスのヒトSLAM利用能獲得に必要な変異 (2013)
  • Author(s): 酒井宏治
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸、日本