Retroviral immune evasion

• Project/Area Number: 25460507
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kinki University
• Principal Investigator: KAWAHARA Sachiyo 近畿大学, 医学部, 講師 (60297629)
• Co-Investigator(Kenkyū-buntansha): MIYAZAWA Masaaki 近畿大学, 医学部, 教授 (60167757) ; TAKAMURA Shiki 近畿大学, 医学部, 医学部講師 (90528564)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: レトロウイルス / TLR7 / B細胞 / 免疫回避 / ウイルス中和抗体 / 白血病 / 中和抗体 / TLR / 自然免疫 / Toll様受容体

Outline of Final Research Achievements

TLR7 is expressed on several types of cell including dendritic cells and B cells. In this study, we analyzed roles of B cell-intrinsic TLR7 signaling on humoral immune responses against retrovirus infection. We found that primary B cell responses to retroviral infection required B cell-intrinsic TLR7 signaling, whereas preexisting virus-specific memory Th cells elicited the B cell responses without TLR7 signaling. Moreover, we showed that in the presence of virus-specific memory Th cells, the lack of TLR7 signaling in B cells facilitated anti-virus antibody responses and led to delayed progression of virus-induced leukemia.

Research Products

• [Journal Article] Erythropoietin receptor antagonist suppressed ectopic hemoglobin synthesis in xenografts of HeLa cells to promote their destruction. (2015)
  • Author(s): Yasuda, Y., Fujita, M., Koike, E., Obata, K., Shiota, M., Kotani, Y., Musha, T., Tsuji-Kawahara, S., Satou, T., Masuda, S, Okano, J., Yamasaki, H., Okumoto, K., Uesugi, T., Nakao, S.,Hoshiai, H. and Mandai, M.
  • Journal Title: PLoS ONE Volume: 10 Issue: 4 Pages: e0122458-e0122458
  • DOI: 10.1371/journal.pone.0122458
  • Peer Reviewed / Open Access
• [Journal Article] Class switch recombination and somatic hypermutation of virus-neutralizing antibodies are not essential for the control of Friend retrovirus infection. (2015)
  • Author(s): Kato, M., S. Tsuji-Kawahara, Y. Kawasaki, S. Kinoshita, T. Chikaishi, S. Takamura, M. Fujisawa, A. Kawada, and M. Miyazawa
  • Journal Title: J. Virol. Volume: 89 Issue: 2 Pages: 1468-1473
  • DOI: 10.1128/jvi.02293-14
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Elimination of Friend retrovirus in the absence of CD8+ T cells (2014)
  • Author(s): Tsuji-Kawahara, S. and M. Miyazawa
  • Journal Title: Journal of Virology Volume: 88 Issue: 3 Pages: 1854-1855
  • DOI: 10.1128/jvi.03271-13
  • Peer Reviewed
• [Journal Article] Infection of adult thymus with murine retrovirus induces virus-specific central tolerance that prevents functional memory CD8+ T cell differentiation (2014)
  • Author(s): Takamura S, Kajiwara E, Tsuji-Kawahara S, Masumoto T, Fujisawa M, Kato M, Chikaishi T, Kawasaki Y, Kinoshita S, Itoi M, Sakaguchi N, Miyazawa M
  • Journal Title: PLoS Pathog Volume: 10 Issue: 3 Pages: e1003937-e1003937
  • DOI: 10.1371/journal.ppat.1003937
  • Peer Reviewed
• [Journal Article] Differential requirements of cellular and humoral immune responses for Fv2-associated resistance to erythroleukemia and for the regulation of retrovirus-induced myeloid leukemia development. (2013)
  • Author(s): Tsuji-Kawahara, S., H. Kawabata, H. Matsukuma, S. Kinoshita, T. Chikaishi, M. Sakamoto, Y. Kawasaki, and M. Miyazawa
  • Journal Title: Journal of Virology Volume: 87 Issue: 24 Pages: 13760-13774
  • DOI: 10.1128/jvi.02506-13
  • Peer Reviewed
• [Journal Article] IFN-γ-producing effector CD8 T lymphocytes cause immune glomerular injury by recognizing antigen presented as immune complex on target tissue. (2013)
  • Author(s): Tsumiyama K, A. Hashiramoto, M. Takimoto, S. Tsuji-Kawahara, M. Miyazawa, and S. Shiozawa
  • Journal Title: The Journal of Immunology Volume: 191 Issue: 1 Pages: 91-96
  • DOI: 10.4049/jimmunol.1203217
  • Peer Reviewed
• [Presentation] B cell-intrinsic TLR7 signaling is required to prevent the generation of recombinant viruses following retrovirus infection (2015)
  • Author(s): Tsuji-Kawahara Sachiyo, Kawasaki Yuri, Motozono Chihiro, Takamura Shiki, Miyazawa Masaaki
  • Organizer: 第44回日本免疫学会
  • Place of Presentation: 札幌コンベンションセンター（札幌市）
  • Year and Date: 2015-11-18
• [Presentation] Vaccine-elicited preferential induction of germinal center follicular helper T cells is associated with protection against retroviral infection (2015)
  • Author(s): Motozono Chihiro, TSUJI-Kawahara Sachiyo, Takamura Shiki, Yagita Hideo, Miyazawa Masaaki
  • Organizer: 第44回日本免疫学会
  • Place of Presentation: 札幌コンベンションセンター（札幌市）
  • Year and Date: 2015-11-18
• [Presentation] Preferential induction of germinal center follicular helper T cells upon retroviral infection in the presence of vaccine-elicited protective CD4 T cells. (2014)
  • Author(s): Motozono C, Tsuji-Kawahara S, Takamura S, Miyazawa M.
  • Organizer: 第43回日本免疫学会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-12-11
• [Remarks] 近畿大学医学部免疫学教室ホームページ
  • URL: http://www.med.kindai.ac.jp/immuno/
• [Remarks] 近畿大学医学部免疫学教室ホームページ
  • URL: http://www.med.kindai.ac.jp/immuno/