九州大学大学院医学研究院

ウイルス学分野

研究内容

1. 肝炎ウイルス研究 

B型肝炎ウイルスの増殖に関与する宿主因子について、検討を進めており、長期的には新規抗ウイルス薬の開発に繋がることを目指しています。宿主因子の同定に関しては、様々なアプローチを行っています。ノックダウンやノックアウトによるスクリーニング、薬剤を用いたスクリーニング、HBV感染細胞や組織を用いたオミクス解析などです。複数の候補因子を同定し、検討を進めています。

また、私たちはC型肝炎の感染指向性に関する研究も行なってきましたが、分子ウイルス学的な解析を継続しております。

  • Kobayashi N, Suzuki S, Sakamoto Y, Suzuki R, Mori K, Kosugi Y, Saito T, Ma Y, Liang L, Izumi T, Noda K, Okuzaki D, Kanegae Y, Hayashi S, Tanaka Y, Yamashita A, Moriishi K, Matsuura Y, Takeuchi O, Tamura T, Taketomi A, Fukuhara T. NEDD4-binding protein 1 suppresses hepatitis B virus replication by regulating viral RNAs. J Gen Virol. 106(3), 2025
  • Fauzyah Y, Ono C, Torii S, Anzai I, Suzuki R, Izumi T, Morioka Y, Maeda Y, Okamoto T, Fukuhara T and Matsuura Y. Ponesimod suppresses hepatitis B virus infection by inhibiting endosome maturation. Antiviral Res. 186; 104999, 2020
  • Ono C, Fukuhara T, Li S, Wang J, Sato A, Izumi T, Fauzyah Y, Yamamoto T, Morioka Y, Dokholyan NV, Standley DM and Matsuura Y. Various miRNAs compensate the role of miR-122 on HCV replication. PLoS Pathog. 16(6): e1008308, 2020
  • Kurihara T, Fukuhara T (Corresponding author), Ono C, Yamamoto S, Uemura K, Okamoto T, Sugiyama M, Motooka D, Nakamura S, Ikawa M, Mizokami M, Maehara Y and Matsuura Y. Suppression of HBV replication by the expression of nickase- and nuclease dead-Cas9. Sci Rep. 7(1): 6122, 2017
  • Ono C, Fukuhara T, Motooka D, Nakamura S, Okuzaki D, Yamamoto S, Tamura T, Mori H, Sato A, Uemura K, Fauzyah Y, Kurihara T, Suda T, Nishio A, Hmwe SS, Okamoto T, Tatsumi T, Takehara T, Chayama K, Wakita T, Koike K and Matsuura Y. Characterization of miR-122-independent propagation of HCV. PLoS Pathog. 13(5): e1006374, 2017
  • Yamamoto S, Fukuhara T, Ono C, Uemura K, Kawachi Y, Shiokawa M, Mori H, Wada M, Shima R, Okamoto T, Hiraga N, Suzuki R, Chayama K, Wakita T and Matsuura Y. Lipoprotein Receptors Redundantly Participate in Entry of Hepatitis C Virus. PLoS Pathog. 12(5): e1005610, 2016
  • Fukuhara T, Wada M, Nakamura S, Ono C, Shiokawa M, Yamamoto S, Motomura T, Okamoto T, Okuzaki D, Yamamoto M, Saito I, Wakita T, Koike K and Matsuura Y. Amphipathic a-helices in apolipoproteins are crucial to the formation of infectious hepatitis C virus particles. PLoS Pathog. 10(12): e1004534, 2014

2. コロナウイルス研究 

2020年に研究室を立ち上げたタイミングは正にコロナ禍が始まった頃でした。コロナウイルス研究の経験はありませんでしたが、ウイルス学者としてできることをと考え、新規リバースジェネティクス系の開発、動物モデルの開発、in vivoイメージング系の開発などを行い、それらを駆使した応用研究も積極的に行いました。2025年現在はポストコロナという言葉も生まれ、ウイルスと人は共存をする世界になっていますが、免疫不全者などCOVID-19が大きなリスクになる集団がいることに加え、次のコロナパンデミックへの備えという意味でも研究を継続することが大事だと考えております。

  • Kondo T, Suzuki R, Yajima H, Kawahara S, Yamaya K, Ichikawa T, Tsujino S, Suzuki S, Tamura T, Hashiguchi T, Fukuhara T. Determinants of susceptibility to SARS-CoV-2 infection in murine ACE2. J Virol. e0054325, 2025
  • Iriyama C, Ichikawa T, Tamura T, Takahata M, Ishio T, Ibata M, Kawai R, Iwata M, Suzuki M, Adachi H, Nao N, Suzuki H, Kawai A, Kamiyama A, Suzuki T, Hirata Y, Iida S, Katano H, Ishii Y, Tsuji T, Oda Y, Tanaka S, Okazaki N, Katayama Y, Nakagawa S, Tsukamoto T, Doi Y, Fukuhara T, Murata T, Tomita A. Clinical and molecular landscape of prolonged SARS-CoV-2 infection with resistance to remdesivir in immunocompromised patients. PNAS Nexus. 4(4): pgaf085, 2025
  • Yamamoto H, Tamura T, Ichikawa T, Taguchi Y, Mori K, Oguri S, Suzuki R, Suzuki S, Teshima T, Fukuhara T. Generation of recombinant viruses directly from clinical specimens of COVID-19 patients. J Clin Microbiol. 62(7): e0004224, 2024
  • Ito H, Tamura T, Wang L, Mori K, Tsuda M, Suzuki R, Suzuki S, Yoshimatsu K, Tanaka S, Fukuhara T. Involvement of SARS-CoV-2 accessory proteins in immunopathogenesis. Microbiol Immunol. 68(7): 237-247, 2024
  • Tamura T, Ito H, Torii S, Wang L, Suzuki R, Tsujino S, Kamiyama A, Oda Y, Tsuda M, Morioka Y, Suzuki S, Shirakawa K, Sato K, Yoshimatsu K, Matsuura Y, Iwano S, Tanaka S, Fukuhara T. Akaluc bioluminescence offers superior sensitivity of track in vivo dynamics of SARS-CoV-2 infection. iScience. 27(5): 109647, 2024
  • Tamura T, Irie T, Deguchi S, Yajima H, Tsuda M, Nasser H, Mizuma K, Plianchaisuk A, Suzuki S, Uriu K, Begum MST M, Shimizu R, Jonathan M, Suzuki R, Kondo T, Ito H, Kamiyama A, Yoshimatsu K, Shofa M, Hashimoto R, Anraku Y, Terakado Kimura K, Kita S, Sasaki J, Sasaki-Tabata K, Maenaka K, Nao N, Wang L, Oda Y, The Genotype to Phenotype Japan (G2P-Japan) Consortium, Ikeda T, Saito S, Matsuno K, Ito J, Tanaka S, Sato K, Hashiguchi T, Takayama K, Fukuhara T. Virological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variant. Nat Commun. 15(1): 1176, 2024
  • Tamura T, Mizuma K, Nasser H, Deguchi S, Padilla-Blanco M, Oda Y, Uriu K, Tolentino JEM, Tsujino S, Suzuki R, Kojima I, Nao N, Shimizu R, Wang L, Tsuda M, Jonathan M, Kosugi Y, Guo Z, Hinay AA Jr, Putri O, Kim Y, Tanaka YL, Asakura H, Nagashima M, Sadamasu K, Yoshimura K; Genotype to Phenotype Japan (G2P-Japan) Consortium; Saito A, Ito J, Irie T, Tanaka S, Zahradnik J, Ikeda T, Takayama K, Matsuno K, Fukuhara T, Sato K. Virological characteristics of the SARS-CoV-2 BA.2.86 variant. Cell Host Microbe. 32(2): 170-180, 2024
  • Ichikawa T, Tamura T, Takahata M, Ishio T, Ibata M, Kasahara I, Minauchi K, Yamamoto S, Teshima T, Fukuhara T. Prolonged shedding of viable SARS-CoV-2 in immunocompromised patients with haematological malignancies: A prospective study. Br J Jaematol, 204(3): 815-820, 2023
  • Tamura T, Yamasoba D, Oda Y, Ito J, Kamasaki T, Nao N, Hashimoto R, Fujioka Y, Suzuki R, Wang L, Ito H, Kashima Y, Kimura I, Kishimoto M, Tsuda M, Sawa H, Yoshimatsu K, Yamamoto Y, Nagamoto T, Kanamune J, Suzuki Y, Ohba Y; Genotype to Phenotype Japan (G2P-Japan) Consortium; Yokota I, Matsuno K, Takayama K, Tanaka S, Sato K, Fukuhara T. Comparative pathogenicity of SARS-CoV-2 Omicron subvariants including BA.1, BA.2, and BA.5. Commun Biol. 6(1): 772, 2023
  • Tomiyama T, Suzuki R, Harada N, Tamura T, Toshida K, Kosai-Fujimoto Y, Tomino T, Yoshiya S, Nagao Y, Takeishi K, Itoh S, Kobayashi M, Ito H, Yoshio S, Kanto T, Yoshizumi T, Fukuhara T. A third dose of the BNT162b2 mRNA vaccine sufficiently improved the neutralizing activity against SARS-CoV-2 variants in liver transplant recipients. Front Cell Infect Microbiol. 13: 1197349, 2023
  • Torii S, Kim KS, Koseki J, Suzuki R, Iwanami S, Fujita Y, Jeong YD, Ito J, Asakura H, Nagashima M, Sadamasu K, Yoshimura K; Genotype to Phenotype Japan (G2P-Japan) Consortium; Sato K, Matsuura Y, Shimamura T, Iwami S, Fukuhara T. Characterization of various remdesivir-resistant mutations of SARS-CoV-2 by mathematical modeling and molecular dynamics simulation. PLoS Pathog. 19(3): e1011231, 2023
  • Saito A, Tamura T, Zahradnik J, Deguchi S, Tabata K, Anraku Y, Kimura I, Ito J, Yamasoba D, Nasser H, Toyoda M, Nagata K, Uriu K, Kosugi Y, Fujita S, Shofa M, Monira Begum M, Shimizu R, Oda Y, Suzuki R, Ito H, Nao N, Wang L, Tsuda M, Yoshimatsu K, Kuramochi J, Kita S, Sasaki-Tabata K, Fukuhara H, Maenaka K, Yamamoto Y, Nagamoto T, Asakura H, Nagashima M, Sadamasu K, Yoshimura K, Ueno T, Schreiber G, Takaori-Kondo A; Genotype to Phenotype Japan (G2P-Japan) Consortium, Shirakawa K, Sawa H, Irie T, Hashiguchi T, Takayama K, Matsuno K, Tanaka S, Ikeda T, Fukuhara T, Sato K. Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant. Cell Host Microbe. 30(11): 1540-1555, 2022
  • Suzuki R, Ono Y, Noshita K, Kim KS, Ito H, Morioka Y, Tamura T, Okuzaki D, Tagawa T, Takenaka T, Yoshizumi T, Shimamura T, Iwami S, Fukuhara T. Smoking Enhances the Expression of Angiotensin-Converting Enzyme 2 Involved in the Efficiency of Severe Acute Respiratory Syndrome Coronavirus 2 Infection. Microbiol Immunol. 67(1): 22-31, 2022
  • Kimura I, Yamasoba D, Tamura T, Nao N, Suzuki T, Oda Y, Mitoma S, Ito J, Nasser H, Zahradnik J, Uriu K, Fujita S, Kosugi Y, Wang L, Tsuda M, Kishimoto M, Ito H, Suzuki R, Shimizu R, Begum MM, Yoshimatsu K, Kimura KT, Sasaki J, Sasaki-Tabata K, Yamamoto Y, Nagamoto T, Kanamune J, Kobiyama K, Asakura H, Nagashima M, Sadamasu K, Yoshimura K, Shirakawa K, Takaori-Kondo A, Kuramochi J, Schreiber G, Ishii KJ; Genotype to Phenotype Japan (G2P-Japan) Consortium, Hashiguchi T, Ikeda T, Saito A, Fukuhara T, Tanaka S, Matsuno K, Sato K. Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants, including BA.4 and BA.5. Cell. 185(21): 3992-4007, 2022
  • Yamasoba D, Kimura I, Nasser H, Morioka Y, Nao N, Ito J, Uriu K, Tsuda M, Zahradnik J, Shirakawa K, Suzuki R, Kishimoto M, Kosugi Y, Kobiyama K, Hara T, Toyoda M, Tanaka YL, Butlertanaka EP, Shimizu R, Ito H, Wang L, Oda Y, Orba Y, Sasaki M, Nagata K, Yoshimatsu K, Asakura H, Nagashima M, Sadamasu K, Yoshimura K, Kuramochi J, Seki M, Fujiki R, Kaneda A, Shimada T, Nakada T, Sakao S, Suzuki T, Ueno T, Takaori-Kondo A, Ishii KJ, Schreiber G, The Genotype to Phenotype Japan (G2P-Japan) Consortium, Sawa H, Saito A, Irie T, Tanaka S, Matsuno K, Fukuhara T, Ikeda T, Sato K. Virological Characteristics of SARS-CoV-2 BA.2 variant. Cell. 185(12): 2103-2115, 2022
  • Suzuki R, Yamasoba D, Kimura I, Wang L, Kishimoto M, Ito J, Morioka Y, Nao N, Nasser H, Uriu K, Kosugi Y, Tsuda M, Orba Y, Sasaki M, Shimizu R, Kawabata R, Yoshimatsu K, Asakura H, Nagashima M, Sadamasu K, Yoshimura K; Genotype to Phenotype Japan (G2P-Japan) Consortium, Sawa H, Ikeda T, Irie T, Matsuno K, Tanaka S, Fukuhara T, Sato K. Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant. Nature. 603(7902): 700-705, 2022
  • Saito A, Irie T, Suzuki R, Maemura T, Nasser H, Uriu K, Kosugi Y, Shirakawa K, Sadamasu K, Kimura I, Ito J, Wu J, Iwatsuki-Horimoto K, Ito M, Yamayoshi S, Loeber S, Tsuda M, Wang L, Ozono S, Butlertanaka EP, Tanaka YL, Shimizu R, Shimizu K, Yoshimatsu K, Kawabata R, Sakaguchi T, Tokunaga K, Yoshida I, Asakura H, Nagashima M, Kazuma Y, Nomura R, Horisawa Y, Yoshimura K, Takaori-Kondo A, Imai M; Genotype to Phenotype Japan (G2P-Japan) Consortium, Tanaka S, Nakagawa S, Ikeda T, Fukuhara T, Kawaoka Y, Sato K. Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation. Nature. 602(7896): 300-306, 2022
  • Torii S, Ono C, Suzuki R, Morioka Y, Anzai I, Fauzyah Y, Maeda Y, Kamitani W, Fukuhara T and Matsuura Y. A novel reverse genetics system for SARS-CoV-2 by using circular polymerase extension reaction. Cell Rep. 35(3): 109014, 2021

3. フラビウイルス研究 

当研究室の武器として、様々な手法を駆使したリバースジェネティクス（ウイルスの人工合成法）があります。フラビウイルスはリバースジェネティクスが困難なウイルスを多く含んでいますが、CPER法を駆使した様々な組換えウイルスを作製し、応用研究を行なっております。フラビウイルスの臓器指向性や病原性発現機構に興味を持って研究を進めています。

  • Tamura T, Yamamoto H, Ogino S, Morioka Y, Tsujino S, Suzuki R, Hiono T, Suzuki S, Isoda N, Sakoda Y, Fukuhara T. A rapid and versatile reverse genetics approach for generating recombinant positive-strand RNA viruses that use IRES-mediated translation. J Virol. 98(3): e0163823, 2024
  • Tamura T, Torii S, Kajiwara K, Anzai I, Fujioka Y, Noda K, Taguwa S, Morioka Y, Suzuki R, Fauzyah Y, Ono C, Ohba Y, Okada M, Fukuhara T, Matsuura Y. Secretory glycoprotein NS1 plays a crucial role in the particle formation of flaviviruses. PLoS Pathog. 18(6): e1010593, 2022
  • Tamura T, Igarashi M, Enkhbold B, Suzuki T, Okamatsu M, Ono C, Mori H, Izumi T, Sato A, Fauzyah Y, Okamoto T, Sakoda Y, Fukuhara T and Matsuura Y. In vivo dynamics of reporter Flaviviridae viruses. J Virol. 93(22): e01191-19, 2019
  • Izumi T, Sakata K, Okuzaki D, Inokuchi S, Tamura T, Motooka D, Nakamura S, Ono C, Shimokawa M, Matsuura Y, Mori M, Fukuhara T and Yoshizumi T. Characterization of human pegivirus infection in liver transplantation recipients. J Med Virol. 91(12): 2093-2100, 2019
  • Tamura T, Fukuhara T, Uchida T, Ono C, Mori H, Sato A, Fauzyah Y, Okamoto T, Kurosu T, Setoh YX, Imamura M, Tautz N, Sakoda Y, Khromykh AA, Chayama K and Matsuura Y. Characterization of recombinant Flaviviridae viruses possessing a small reporter tag. J Virol. 92(2): e01582-17, 2018
  • Fukuhara T, Tamura T, Ono C, Shiokawa M, Mori H, Uemura K, Yamamoto S, Kurihara T, Okamoto T, Suzuki R, Yoshii K, Kurosu T, Igarashi M, Aoki H, Sakoda Y and Matsuura Y. Host-derived apolipoproteins play comparable roles with viral secretory proteins Erns and NS1 in the infectious particle formation of Flaviviridae. PLoS Pathog. 13(6): e1006475, 2017

4. RSウイルス研究

新型コロナウイルス研究を行う中で、当研究室では新規リバースジェネティクス手法の構築や呼吸器ウイルスの感染モデルの開発を進めました。2024年度よりその技術をRSウイルスにも応用して、メインの研究の1つとして進めることにしました。