Studies on influenza A virus M2-host interactome and its role in virus replication

• Project/Area Number: 16K08014
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Hokkaido University
• Principal Investigator: Manzoor Rashid 北海道大学, 人獣共通感染症リサーチセンター, 特任助教 (90566150)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: influenza A virus / M2 protein / Influenza A virus / M2 / Host interaction / influenza / host factor

Outline of Final Research Achievements

Despite the diverse roles of IAV-M2 during virus replication, little is known about the molecular basis of these diverse functions. While en route to the cell membrane, the M2-ectodomain and cytoplasmic tail are exposed to vesicular/organelle and cytoplasmic environments, where they may interact with various cellular proteins. During this study we identified host-proteins which interact with IAV M2 protein and affect virus replication. We found two amino acid residues (position 54 and 57) uniquely different between two IAV subtypes that governed the interaction of M2 with plasma membrane thereby playing role in virus budding/release. The M2 protein, besides increasing the transmembrane domain (TMD) length and having two inherent lipid raft targeting features, did not associate with lipid rafts suggesting that　the M2-TMD length is not the only non-lipid micro-domain localization determinant. These results also suggested that virus release/budding requires optimum length of M2-TMD.

Academic Significance and Societal Importance of the Research Achievements

Our findings add significant information to the existing scientific knowledge on influenza A virus M2 protein roles in virus infected cells, plausibly providing the basic information that can be used for the development of strategies for virus control and therapeutic measures.

Research Products

• [Journal Article] A potential role of non-neutralizing IgA antibodies in cross-protective immunity against influenza A viruses of multiple hemagglutinin subtypes (2020)
  • Author(s): Okuya K, Yoshida R, Manzoor R, Saito S, Suzuki T, Sasaki M, Saito T, Kida Y, Mori-Kajihara A, Kondoh T, Sato M, Kajihara M, Miyamoto H, Ichii O, Higashi H, Takada A
  • Journal Title: J Virol Volume: - Issue: 12 Pages: 408-420
  • DOI: 10.1128/jvi.00408-20
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Generation of bat-derived influenza viruses and their reassortants (2019)
  • Author(s): Sato Masahiro、Maruyama Junki、Kondoh Tatsunari、Nao Naganori、Miyamoto Hiroko、Takadate Yoshihiro、Furuyama Wakako、Kajihara Masahiro、Ogawa Hirohito、Manzoor Rashid、Yoshida Reiko、Igarashi Manabu、Takada Ayato
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 1158-1158
  • DOI: 10.1038/s41598-018-37830-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Influenza A Virus M2 Protein: Roles from Ingress to Egress (2017)
  • Author(s): Manzoor Rashid、Igarashi Manabu、Takada Ayato
  • Journal Title: International Journal of Molecular Sciences Volume: 18 Issue: 12 Pages: 2649-2649
  • DOI: 10.3390/ijms18122649
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genetic predisposition to acquire a polybasic cleavage site for highly pathogenic avian influenza virus hemagglutinin (2017)
  • Author(s): Nao N, Yamagishi J, Miyamoto H, Igarashi M, Manzoor R, Ohnuma A, Tsuda Y, Furuyama W, Shigeno A, Kajihara M, Kishida N, Yoshida R, Takada A
  • Journal Title: MBio Volume: 8 Issue: 1 Pages: 1-15
  • DOI: 10.1128/mbio.02298-16
  • NAID: 120006337761
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Mechanism of antiviral activity of an M2 ectodomain-specific monoclonal antibody against influenza A virus (2018)
  • Author(s): Manzoor Rashid
  • Organizer: 17th NSV (Negative Strand Viruses)
  • Int'l Joint Research
• [Presentation] Inhibitory effects of an M2 ectodomain-specific monoclonal antibody against different influenza A virus strains (2017)
  • Author(s): Manzoor Rashid
  • Organizer: The 65th Annual Meeting of the Japanese Society for Virology
  • Int'l Joint Research
• [Presentation] Role of transmembrane domain of influenza A virus M2 protein in determining association with membrane microdomains (2017)
  • Author(s): Manzoor Rashid
  • Organizer: International Union of Microbiological Societies Congress (IUMS), 17th International Congress of Virology
  • Int'l Joint Research
• [Presentation] Identifying and dissecting the role of host factors interacting with influen za A virus M2 protein in influenza virus replication (2016)
  • Author(s): Manzoor Rashid
  • Organizer: The 15th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awaji Yumebutai International Conference Center
  • Year and Date: 2016-09-06
• [Remarks] 北海道大学人獣共通感染症リサーチセンター国際疫学部門
  • URL: http://www.czc.hokudai.ac.jp/en/research/epidemiology/
• [Remarks] 北海道大学人獣共通感染症リサーチセンター国際疫学部門
  • URL: http://www.czc.hokudai.ac.jp/research/epidemiology/