Molecular mechanisms underlying antibody-mediated inhibition of virus budding

• Project/Area Number: 25892002
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Veterinary medical science
• Research Institution: Hokkaido University
• Principal Investigator: KAJIHARA Masahiro 北海道大学, 人獣共通感染症リサーチセンター, 研究員 (70711894)
• Project Period (FY): 2013-08-30 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: フィロウイルス / エボラウイルス / マールブルグウイルス / 出芽 / 抗体 / 表面糖蛋白質 / エボラウイルス病 / マールブルグ熱 / エボラ出血熱

Outline of Final Research Achievements

Previously, we reported antibody-mediated inhibition of virus budding from infected cells. However, the molecular basis and contribution to protective immunity of antibody-mediated budding inhibition are yet unknown. We found that antibodies induced by nasal immunization had inhibitory activity of influenza virus release from infected cells. It was morphologically suggested that the progeny virions were deposited on the infected cell surface by the tethering mediated by IgA antibody binding, which may be the molecular basis of cross-protective immunity induced by nasal immunization. We examined the involvement of budding inhibition antibodies in protective immunity through passive immunization of hamsters against Marburg virus infection. Immunization with budding inhibition antibody slightly improved clinical outcomes of infected hamsters, indicating that budding inhibition antibodies are also involved in protective immunity.

Research Products

• [Journal Article] The Interaction between TIM-1 and NPC1 is important for the cellular entry of Ebola virus (2015)
  • Author(s): Kuroda M, Fujikura D, Nanbo A, Marzi A, Noyori O, Kajihara M, Maruyama J, Matsuno K, Miyamoto H, Yoshida R, Feldmann H, Takada A
  • Journal Title: J. Virol. Volume: 印刷中 Issue: 12 Pages: 6481-6493
  • DOI: 10.1128/jvi.03156-14
  • NAID: 120005621883
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Seroepidemiological prevalence of multiple species of filoviruses in fruit bats (Eidolon helvum) migrating in Africa. (2015)
  • Author(s): Hirohito Ogawa, Hiroko Miyamoto, Eri Nakayama, Reiko Yoshida, Ichiro Nakamura, Hirofumi Sawa, Akihiro Ishii, Yuka Thomas, Emiko Nakagawa, Keita Matsuno, Masahiro Kajihara, Junki Maruyama, Manabu Igarashi, Kimihito Ito, Ayato Takada et al
  • Journal Title: Journal of Infectious Diseases Volume: jiv063 Issue: suppl 2 Pages: S101-S108
  • DOI: 10.1093/infdis/jiv063
  • Peer Reviewed / Open Access
• [Journal Article] Pathological and molecular diagnosis of the 2013 African swine fever outbreak in Lusaka, Zambia (2015)
  • Author(s): Yabe J, Hamambulu P, Simulundu E, Ogawa H, Kajihara M, Mori-Kajihara A, Changula-Chitanga K, Mwase M, Mweemba-Muwowo M, Chambaro HM, Mataa L, Hang'ombe B, Namangala B, Fandamu P, Sawa H, Takada A, Higashi H, Mweene AS.
  • Journal Title: Trop Anim Health Prod Volume: 47 Issue: 2 Pages: 459-463
  • DOI: 10.1007/s11250-014-0732-0
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive molecular detection of tick-borne phleboviruses leads to the retrospective identification of taxonomically unassigned bunyaviruses and the discovery of a novel member of the genus phlebovirus (2015)
  • Author(s): Matsuno K, Weisend C, Kajihara M, Matysiak C, Williamson BN, Simuunza M, Mweene AS, Takada A, Tesh RB, Ebihara H
  • Journal Title: Journal of Virology Volume: 89 Issue: 1 Pages: 594-604
  • DOI: 10.1128/jvi.02704-14
  • Peer Reviewed
• [Journal Article] Host Cell Factors Involved in Filovirus Infection (2014)
  • Author(s): Masahiro Kajihara, Ayato Takada
  • Journal Title: Curr. Trop. Med. Rep. Volume: 2 Issue: 1 Pages: 30-40
  • DOI: 10.1007/s40475-015-0039-x
  • Peer Reviewed / Open Access
• [Journal Article] A polymorphism of the TIM-1 IgV domain: Implications for the susceptibility to filovirus infection. (2014)
  • Author(s): Makoto Kuroda, Daisuke Fujikura, Osamu Noyori, Masahiro Kajihara, Junki Maruyama, Hiroko Miyamoto, Reiko Yoshida, Ayato Takada.
  • Journal Title: Biochemical and biophysical research communications Volume: 455 Issue: 3-4 Pages: 223-228
  • DOI: 10.1016/j.bbrc.2014.10.144
  • Peer Reviewed / Open Access
• [Journal Article] Ebola and Marburg virus diseases in Africa: Increased risk of outbreaks in previously unaffected areas? (2014)
  • Author(s): Changula K, Kajihara M, Mweene AS, Takada A
  • Journal Title: Microbiol. Immunol. Volume: 58 Issue: 9 Pages: 483-491
  • DOI: 10.1111/1348-0421.12181
  • Peer Reviewed / Open Access
• [Journal Article] The zoonotic potential of avian influenza viruses isolated from wild waterfowl in Zambia (2014)
  • Author(s): Simulundu E, Nao N, Yabe J, Muto NA, Sithebe T, Sawa H, Manzoor R, Kajihara M, Muramatsu M, Ishii A, Ogawa H, Mweene AS, Takada A
  • Journal Title: Archives of Virology Volume: 159 Issue: 10 Pages: 2633-2640
  • DOI: 10.1007/s00705-014-2124-1
  • NAID: 120005656330
  • Peer Reviewed
• [Journal Article] Mapping of conserved and species-specific antibody epitopes on the Ebola virus nucleoprotein. (2013)
  • Author(s): Changula Katendi
  • Journal Title: Virus Res. Volume: 176 Issue: 1-2 Pages: 83-90
  • DOI: 10.1016/j.virusres.2013.05.004
  • Peer Reviewed
• [Journal Article] Heterosubtypic antiviral activity of hemagglutinin-specific antibodies induced by intranasal immunization with inactivated influenza viruses in mice. (2013)
  • Author(s): Muramatsu M. et al.
  • Journal Title: PLoS One Volume: 8 Issue: 8 Pages: e71534-e71534
  • DOI: 10.1371/journal.pone.0071534
  • Peer Reviewed
• [Journal Article] Differential potential for envelope gycoprotein-mediated steric shielding of host cell surface proteins among filoviruses (2013)
  • Author(s): Noyori Osamu
  • Journal Title: Virology Volume: 446 Issue: 1-2 Pages: 152-161
  • DOI: 10.1016/j.virol.2013.07.029
  • Peer Reviewed
• [Journal Article] Characterization of the envelope glycoprotein of a novel filovirus, Lloviu virus (2013)
  • Author(s): Maruyama J, Miyamoto H, Kajihara M, Ogawa H, Maeda K, Sakoda Y, Yoshida R, Takada A
  • Journal Title: J. Virol. Volume: 88 Issue: 1 Pages: 99-109
  • DOI: 10.1128/jvi.02265-13
  • NAID: 120005451570
  • Peer Reviewed
• [Journal Article] Comparison of Antiviral Activity between IgA and IgG Specific to Influenza Virus Hemagglutinin: Increased Potential of IgA for Heterosubtypic Immunity (2013)
  • Author(s): Muramatsu M, Yoshida R, Yokoyama A, Miyamoto H, Kajihara M, Maruyama J, Nao N, Manzoor R, Takada A
  • Journal Title: PLoS ONE Volume: 9 Issue: 1 Pages: e85582-e85582
  • DOI: 10.1371/journal.pone.0085582
  • NAID: 120005425353
  • Peer Reviewed
• [Journal Article] Heat Shock Protein 70 Modulates Influenza A Virus Polymerase Activity (2013)
  • Author(s): Manzoor R, Kuroda K, Yoshida R, Tsuda Y, Fujikura D, Miyamoto H, Kajihara M, Kida H, Takada A
  • Journal Title: J. Biol. Chem. Volume: 289 Issue: 11 Pages: 7599-7614
  • DOI: 10.1074/jbc.m113.507798
  • NAID: 120005460233
  • Peer Reviewed
• [Presentation] A 型インフルエンザウイルスヘマグルチニン特異的IgA 抗体の亜型間交差抗ウイルス活性 (2014)
  • Author(s): 村松美笑子、吉田玲子、横山文香、宮本洋子、梶原将大、丸山隼輝、直享則、 Rashid Manzoor、高田礼人
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜会議センター（横浜市）
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] フィロウイルスの細胞侵入におけるTIM 1 とNPC1 相互作用の解析 (2014)
  • Author(s): 黒田誠、藤倉大輔、南保明日香、野依修、梶原将大、丸山隼輝、宮本洋子、 吉田玲子、高田礼人
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜会議センター（横浜市）
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] Neutralizing Monoclonal Antibody therapy for H5N1 Highly Pathogenic Avian Influenza virus infection in Animal Models (2014)
  • Author(s): Muramatsu M, Yoshida R, Yokoyama A, Miyamoto H, Kajihara M, Maruyama J, Nao N, Manzoor R, Takada A
  • Organizer: The 13th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Nara Prefectural New Public Hall (Nara)
  • Year and Date: 2014-09-23 – 2014-09-26
• [Presentation] Correlates of Hsp70 kinetics and influenza A virus polymerase activity (2014)
  • Author(s): Manzoor R, Kuroda K, Yoshida R, Tsuda Y, Fujikura D, Miyamoto H, Kajihara M, Kida H, Takada A
  • Organizer: The 13th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Nara Prefectural New Public Hall (Nara)
  • Year and Date: 2014-09-23 – 2014-09-26
• [Presentation] 北海道産マダニからの新規フレボウイルスの検出 (2014)
  • Author(s): 中尾亮、梶原将大、邱永晋、森亜紀奈、直亨則、村松美笑子、好井健太朗、苅和宏明、澤洋文、杉本千尋、高田礼人
  • Organizer: 第157回日本獣医学会学術集会
  • Place of Presentation: 北海道大学（札幌市）
  • Year and Date: 2014-09-09 – 2014-09-12
• [Presentation] Detection and isolation of novel phleboviruses from ticks in Japan (2014)
  • Author(s): Nakao R, Kajihara M, Matsuno K, Qiu Y, Mori A, Nao N, Yoshii K, Kariwa H, Sawa H, Sugimoto C, Takada A, Ebihara H
  • Organizer: VIII International Conference on Ticks and Tick-borne Pathogens
  • Place of Presentation: Cape Town (South Africa)
  • Year and Date: 2014-08-24 – 2014-08-29
• [Presentation] Characterization of the envelope glycoprotein of a novel filovirus, Lloviu virus (2014)
  • Author(s): Maruyama J, Miyamoto H, Kajihara M, Ogawa H, Maeda K, Sakoda Y, Yoshida R, Takada A
  • Organizer: XVI International Congress of Virology
  • Place of Presentation: Montreal (Canada)
  • Year and Date: 2014-07-27 – 2014-08-01
• [Presentation] A polymorphism in TIM‐1 is associated with cell susceptibility to filovirus infection (2014)
  • Author(s): Kuroda M, Fujikura D, Noyori O, Nakayama E, Kajihara M, Maruyama J, Miyamoto H, Yoshida R, Takada A
  • Organizer: XVI International Congress of Virology
  • Place of Presentation: Montreal (Canada)
  • Year and Date: 2014-07-27 – 2014-08-01
• [Presentation] Different pathogenicity of H5N1 highly pathogenic avian influenza viruses determined by a single amino acid in the M1 protein (2014)
  • Author(s): Nao N, Kajihara M, Maruyama J, Kimura T, Manzoor R, Muramatsu M, Yoshida R, Okamatsu M, Kida H, Takada A
  • Organizer: XVI International Congress of Virology
  • Place of Presentation: Montreal (Canada)
  • Year and Date: 2014-07-27 – 2014-08-01
• [Presentation] フィロウイルス感受性に及ぼすTIM-1多型の影響 (2013)
  • Author(s): 黒田誠、藤倉大輔、野依修、中山絵里、梶原将大、丸山隼輝、宮本洋子、吉田玲子、高田礼人
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸国際会議場 (神戸市)
• [Presentation] 2010年に稚内で分離された2株の高病原性鳥インフルエンザウイルスの病原性比較 (2013)
  • Author(s): 直亨則、梶原将大、丸山隼輝、木村享史、Manzoor Rashid、村松美笑子、岡松正敏、宮本洋子、吉田玲子、迫田義博、喜田宏、高田礼人
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸国際会議場 (神戸市)
• [Book] 生体の科学 (2015)
  • Author(s): 梶原将大、髙田礼人
  • Publisher: 医学書院
• [Book] 実験医学 (2015)
  • Author(s): 梶原将大
  • Total Pages: 3
  • Publisher: 羊土社
• [Book] 実験医学 第31巻 第19号 (2013)
  • Author(s): 梶原将大、小川寛人、高田礼人
  • Publisher: 羊土社