Analyses of arenavirus cell entry mechanisms including novel entry factors

• Project/Area Number: 24790451
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: TANI Hideki 国立感染症研究所, ウイルス第一部, 主任研究官 (20397706)
• Project Period (FY): 2012-04-01 – 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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 細胞侵入機構 / アレナウイルス / ルジョウイルス / NPC-1 / 細胞侵入 / シュードタイプウイルス / PDGFR

Outline of Final Research Achievements

Several arenaviruses are known to cause viral hemorrhagic fever (VHF) in Sub-Saharan Africa and South America, where VHF is a major public health and medical concern. The biosafety level four categorization of these arenaviruses restricts their use and has impeded biological studies, including therapeutic drug and/or vaccine development. Due to difficulties associated with handling live viruses, pseudotype viruses, which transiently bear arenavirus envelope proteins based on vesicular stomatitis virus (VSV), have been developed as surrogate virus systems. In this study, we developed a pseudotype VSV bearing each envelope protein of various species of arenaviruses, including the newly identified Lujo virus (LUJV) and Chapare virus. We found that LUJpv utilizes neither αDG nor hTfR1 as receptor and unique characteristics of LUJV glycoprotein in membrane fusion and cell entry. Proper exclusion of cholesterol or some kinds of lipids may play important roles in the LUJpv cell entry.

Research Products

• [Journal Article] Development and validation of serological assays for viral hemorrhagic fevers and determination of the prevalence of Rift Valley fever in Borno State, Nigeria. (2014)
  • Author(s): David N. Bukbuk, Shuetsu Fukushi, Hideki Tani, Tomoki Yoshikawa, Satoshi Taniguchi, Koichiro Iha, Aiko Fukuma, Masayuki Shimojima, Shigeru Morikawa, Masayuki Saijo, F. Kasolo, S.S. Baba
  • Journal Title: Transactions of the Royal Society of Tropical Medicine & Hygiene Volume: 108 Issue: 12 Pages: 768-773
  • DOI: 10.1093/trstmh/tru163
  • Peer Reviewed
• [Journal Article] Effects of ribavirin on severe Fever with thrombocytopenia syndrome virus in vitro. (2014)
  • Author(s): Masayuki Shimojima, Shuetsu Fukushi, Hideki Tani, Tomoki Yoshikawa, Aiko Fukuma, Satoshi Taniguchi, Yuto Suda, Ken Maeda, Toru Takahashi, Shigeru Morikawa, Masayuki Saijo
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 67 Pages: 423-427
  • NAID: 130004712732
  • Peer Reviewed / Open Access
• [Journal Article] Analyses of Entry Mechanisms of Novel Emerging Viruses Using Pseudotype VSV System (2014)
  • Author(s): Hideki Tani
  • Journal Title: Tropical Medicine and Health Volume: 42 Issue: 2SUPPLEMENT Pages: S71-S82
  • DOI: 10.2149/tmh.2014-S10
  • NAID: 130004463468
  • ISSN: 1348-8945, 1349-4147
  • Open Access
• [Journal Article] 重症熱性血小板減少症候群（SFTS） (2014)
  • Author(s): 谷 英樹
  • Journal Title: 臨床と微生物 Volume: 41 Pages: 45-49
• [Journal Article] 重症熱性血小板減少症候群（SFTS） (2014)
  • Author(s): 谷 英樹、西條政幸
  • Journal Title: 血液フロンティア Volume: 24 Pages: 80-83
• [Journal Article] Analysis of Lujo virus cell entry using pseudotype vesicular stomatitis virus (2014)
  • Author(s): Hideki Tani, Koichiro Iha, Masayuki Shimojima, Shuetsu Fukushi, Satoshi Taniguchi, Tomoki Yoshikawa, Yoshihiro Kawaoka, Naoe Nakasone, Haruaki Ninomiya, Masayuki Saijo, and Shigeru Morikawa
  • Journal Title: Journal of Virology Volume: 88 Issue: 13 Pages: 7317-7330
  • DOI: 10.1128/jvi.00512-14
  • Peer Reviewed
• [Journal Article] アレナウイルス感染症 (2013)
  • Author(s): 谷 英樹、福士秀悦、吉河智城、西條政幸、森川茂
  • Journal Title: ウイルス Volume: 62 Pages: 229-238
  • NAID: 10031140222
• [Journal Article] Serological assays based on recombinant viral proteins for the diagnosis of arenavirus hemorrhagic fevers (2012)
  • Author(s): Shuetsu Fukushi, Hideki Tani, Tomoki Yoshikawa, Masayuki Saijo, and Shigeru Morikawa
  • Journal Title: Viruses Volume: 4 Issue: 10 Pages: 2097-2114
  • DOI: 10.3390/v4102097
  • Peer Reviewed
• [Journal Article] Specific interaction of the envelope glycoproteins E1 and E2 with liver heparan sulfate involved in the tissue tropismatic infection by hepatitis C virus (2012)
  • Author(s): Kobayashi, F., Yamada, S., Taguwa, S., Naito, S., Tani, H., Matsuura, Y., and Sugahara, K.
  • Journal Title: Glycoconjugate Journal Volume: 29 Issue: 4 Pages: 211-220
  • DOI: 10.1007/s10719-012-9388-z
  • Peer Reviewed
• [Presentation] Entry and Fusion Mechanisms of SFTSV. (2015)
  • Author(s): Hideki Tani
  • Organizer: 17th International Conference on Emerging Infectious Diseases
  • Place of Presentation: Taiwan
  • Year and Date: 2015-01-28 – 2015-01-29
  • Invited
• [Presentation] 重症熱性血小板減少症候群ウイルスGPの細胞融合能と25-hydroxycholesterolによる感染阻害効果 (2014)
  • Author(s): 谷 英樹、谷口 怜、福間藍子、福士秀悦、森川 茂、下島昌幸、西條政幸
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] Analyses of cell entry of severe fever with thrombocytopenia syndrome virus using pseudotype vesicular stomatitis virus system. (2014)
  • Author(s): Hideki Tani, Masayuki Shimojima, Shuetsu Fukushi, Tomoki Yoshikawa, Aiko Fukuma, Satoshi Taniguchi, Momoko Ogata, Shigeru Morikawa, Masayuki Saijo
  • Organizer: XVI International Congress of Virology
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2014-07-27 – 2014-08-01
• [Presentation] Analysis of cell entry of a novel arenavirus, Lujo virus, using pseudotype VSV (2013)
  • Author(s): Hideki Tani, Masayuki Shimojima, Shuetsu Fukushi, Tomoki Yoshikawa, Masayuki Saijo, and Shigeru Morikawa
  • Organizer: XV International Conference on Negative Strand Viruses
  • Place of Presentation: Granada, Spain
• [Presentation] Analyses of entry mechanisms of novel emerging viruses using pseudotype VSV system (2013)
  • Author(s): Hideki Tani
  • Organizer: The 54th Annual Meeting for the Japanese Society of Tropical Medicine
  • Place of Presentation: Nagasaki
  • Invited
• [Presentation] 重症熱性血小板減少症候群ウイルスGPを外套したシュードタイプVSVの作製 (2013)
  • Author(s): 谷 英樹、下島昌幸、福間藍子、谷口 怜、吉河智城、福士秀悦、森川 茂、前田 健、高橋 徹、西條政幸
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸
• [Presentation] Characterization of New and Old World arenavirus glycoprotein-mediated entry (2013)
  • Author(s): Hideki Tani, Masayuki Shimojima, Shuetsu Fukushi, Tomoki Yoshikawa, Masayuki Saijo, and Shigeru Morikawa
  • Organizer: 15th International Conference on Emerging Infectious Diseases in the Pacific Rim
  • Place of Presentation: Shingapore
  • Invited
• [Presentation] Characterization of pseudotype VSV possessing New and Old World arenavirus envelope proteins (2012)
  • Author(s): Hideki Tani, Koichiro Iha, Shuetsu Fukushi, Satoshi Taniguchi, Tomoki Yoshikawa, Masayuki Saijo, and Shigeru Morikawa
  • Organizer: The 11th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awaji Yumebutai International Conference Center, Hyogo, Japan
• [Presentation] Serological assays based on recombinant viral proteins for the diagnosis of viral hemorrhagic fevers caused by arenaviruses (2012)
  • Author(s): Kie Yamamoto, Koichiro Iha, Satoshi Taniguchi, Shuetsu Fukushi, Hideki Tani, Tomoki Yoshikawa, Shigeru Kyuwa, Roger Hewson, Masayuki Saijo, and Shigeru Morikawa
  • Organizer: XVIII International Congress for Tropical Medicine and Malaria
  • Place of Presentation: Rio de Janeiro, Brazil
• [Presentation] Analysis of cell entry of New and Old World arenaviruses using pseudotyped viruses bearing their envelope proteins (2012)
  • Author(s): Hideki Tani, Koichiro Iha, Shuetsu Fukushi, Satoshi Taniguchi, Tomoki Yoshikawa, Masayuki Saijo, and Shigeru Morikawa
  • Organizer: XVIII International Congress for Tropical Medicine and Malaria
  • Place of Presentation: Rio de Janeiro, Brazil
• [Presentation] シュードタイプVSVを用いたルジョウイルスの細胞侵入機構の解析 (2012)
  • Author(s): 谷 英樹、伊波興一朗、谷口 怜、吉河智城、福士秀悦、西條政幸、森川 茂
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪国際会議場、大阪