Development of anti-HIV agents that exert synergism with host immune pressure
Project/Area Number |
24390254
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Infectious disease medicine
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Research Institution | Tohoku University |
Principal Investigator |
KODAMA Eiichi 東北大学, 医学(系)研究科(研究院), 講師 (50271151)
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Co-Investigator(Kenkyū-buntansha) |
UENO Takamasa 熊本大学, エイズ学研究センター, 准教授 (10322314)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2014: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2012: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
|
Keywords | HIV / 抗ウイルス剤 / 免疫淘汰 / スクリーニング / アクセサリータンパク / HIV |
Outline of Final Research Achievements |
Treatment of HIV, so far, remains to be insufficient. Therefore, development of efficient and safe therapy for HIV infection is urgently needed. Here, we focus on one of essential accessary viral proteins, Nef that has povital role in escape from host immune system, through immunological, rational drug design, and structural features. We newly identified novel domains for down regulation of MHC class I, and HIV receptors CD4 and CCR5, and established a screening system for Nef antagonists. Furthermore, we revealed impaired Nef functions in the elite controllers. Our findings will provide insights into further successful therapies and development of effective vaccines.
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Report
(4 results)
Research Products
(42 results)
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[Journal Article] Inhibition of the DNA polymerase and RNase H activities of HIV-1 reverse transcriptase and HIV-1 replication by Brasenia schreberi (Junsai) and Petasites japonicus (Fuki) components.2015
Author(s)
Tetsuro Hisayoshi, Mayu Shinomura, Kanta Yokokawa, Ikumi Kuze, Atsushi Konishi, Kumi Kawaji, Eiichi N. Kodama, Keishi Hata, Saori Takahashi, Satoru Nirasawa, Kiyoshi Yasukawa.
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Journal Title
Journal of Natural Medicines
Volume: in press
Issue: 3
Pages: 432-440
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Modest Attenuation of HIV-1 Vpu Alleles Derived from Elite Controller Plasma.2015
Author(s)
Chen J, Tibroni N, Sauter D, Galaski J, Miura T, Alter G, Mueller B, Haller C, Walker BD, Kirchhoff F, Brumme ZL, Ueno T, Fackler OT.
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Journal Title
PLoS One
Volume: 10
Issue: 3
Pages: e0120434-e0120434
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] 4’-Ethynyl-2-fluoro-2’-deoxyadenosine (EFdA) inhibits HIV-1 reverse transcriptase with multiple mechanisms.2014
Author(s)
Eleftherios Michailidis, Andrew D. Huber, Emily M. Ryan, Yee T. Ong, Maxwell D. Leslie, Kayla B. Matzek, Kamalendra Singh, Bruno Marchand, Ariel N. Hagedorn, Karen A. Kirby, Lisa C. Rohan, Eiichi N. Kodama, Hiroaki Mitsuya, Michael A. Parniak, and Stefan G. Sarafianos.
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Journal Title
Journal of Biological Chemistry
Volume: 289
Issue: 35
Pages: 24533-24548
DOI
Related Report
Peer Reviewed
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[Journal Article] Impaired Nef function is associated with early control of HIV-1 viremia.2014
Author(s)
Kuang XT, Li X, Anmole G, Mwimanzi P, Shahid A, Le AQ, Chong L, Qian H, Miura T, Markle T, Baraki B, Connick E, Daar ES, Jessen H, Kelleher AD, Little S, Markowitz M, Pereyra F, Rosenberg ES, Walker BD, Ueno T, Brumme ZL, Brockman MA.
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Journal Title
Journal of Virology
Volume: 88
Issue: 17
Pages: 10200-10213
DOI
Related Report
Peer Reviewed
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[Journal Article] Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design.2013
Author(s)
Izumi K, Kawaji K, Miyamoto F, Shimane K, Shimura K, Sakagami Y, Hattori T, Watanabe K, Oishi S, Fujii N, Matsuoka M, Kaku M, Sarafianos SG, Kodama EN.
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Journal Title
Int J Biochem Cell Biol.
Volume: 45
Issue: 4
Pages: 908-915
DOI
Related Report
Peer Reviewed
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[Journal Article] HIV-1 resistance mechanism to an electrostatically constrained peptide fusion inhibitor that is active against T-20-resistant strains.2013
Author(s)
Kazuki Shimane, KumiKawaji, Fusako Miyamoto, Shinya Oishi, Kentaro Watanabe, YasukoSakagami, Nobutaka Fujii, Kazuya Shimura, Masao Matsuoka, Mitsuo Kaku, Stefan Sarafianos, and Eiichi Kodama
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Journal Title
Antimicrobal Agents and Chemotherapy
Volume: 57
Issue: 8
Pages: 4035-4038
DOI
Related Report
Peer Reviewed
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[Journal Article] Hypersusceptibility Mechanism of Tenofovir-Resistant HIV to EFdA2013
Author(s)
Eleftherios Michailidis, Emily M Ryan, Atsuko Hachiya, Karen A Kirby, Bruno Marchand, Maxwell D Leslie, Andrew D Huber, Yee T Ong, Jacob C Jackson, Kamalendra Singh, Eiichi N Kodama, Hiroaki Mitsuya, Michael A Parniak and Stefan G Sarafianos
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Journal Title
Retrovirology
Volume: 10
Issue: 1
Pages: 65-65
DOI
Related Report
Peer Reviewed
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[Journal Article] Evaluation of combinations of 4'-ethynyl-2-fluoro-2'-deoxyadenosine with clinically used antiretroviral drugs.2013
Author(s)
Atsuko Hachiya, Aaron Reeve, Bruno Marchand, Eleftherios Michailidis, Yee Ong, Karen Kirby, Maxwell Leslie, Shinichi Oka, Eiichi Kodama, Lisa Rohan, Hiroaki Mitsuya, Michael Parniak, and Stefan Sarafianos
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Journal Title
Antimicrobal Agents and Chemotherapy
Volume: 57
Pages: 4554-4558
Related Report
Peer Reviewed
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[Journal Article] Effects of substitutions at the 4' and 2 positions on the bioactivity of 4'-ethynyl-2-fluoro-2'-deoxyadenosine2013
Author(s)
Kirby KA, Michailidis E, Fetterly TL, Steinbach MA, Singh K, Marchand B, Leslie MD, Hagedorn AN, Kodama EN, Marquez VE, Hughes SH, Mitsuya H, Parniak MA, Sarafianos SG.
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Journal Title
Antimicrobal Agents and Chemotherapy
Volume: 57
Issue: 12
Pages: 6254-6264
DOI
Related Report
Peer Reviewed
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[Journal Article] Attenuation of multiple Neffunctions in HIV-1 elite controllers2013
Author(s)
Philip Mwimanzi, Tristan J Markle,Eric Martin, Yoko Ogata, Xiaomei TKuang, Michiyo Tokunaga, MacdonaldMahiti, Florencia Pereyra, ToshiyukiMiura, Bruce D Walker, Zabrina L Brumme,Mark A Brockman and *Takamasa Ueno
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Journal Title
Retrovirology
Volume: 10
Issue: 1
Pages: 1-1
DOI
Related Report
Peer Reviewed
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[Journal Article] Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design.2013
Author(s)
Kazuki Izumi, Kumi Kawaji, Fusasko Miyamoto, Kazuki Shimane, Kazuya Shimura, Yasuko Sakagami, Toshio Hattori, Kentaro Watanabe, Shinya Oishi, Nobutaka Fujii, Masao Matsuoka, Mitsuo Kaku, Stefan G. Sarafianos, and Eiichi N. Kodama
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Journal Title
Int. J. Biovjem. Cell Biol.
Volume: 45
Pages: 908-915
Related Report
Peer Reviewed
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[Journal Article] Biochemical, inhibition, and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase.2012
Author(s)
TP. Ndongwe, AO. Adedeji, E Michailidis, YT Ong, A Hachiya, B Marchand, EM. Ryan, DK. Rai, KA. Kirby, AS. Whatley, DH. Burke, M Johnson, S Ding, YM Zheng, SL Liu, E Kodama, KA. Delviks-Frankenberry, VK. Pathak, H Mitsuya, MA. Parniak, K Singh, SG. Sarafianos.
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Journal Title
Nucleic Acids Research
Volume: 40
Pages: 345-359
Related Report
Peer Reviewed
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[Journal Article] HIV-1 reverse transcriptase (RT) polymorphism 172K suppresses the effect of clinically relevant drug resistance mutations to both nucleoside and non-nucleoside RT inhibitors.2012
Author(s)
Hachiya A, Marchand B, Kirby KA, Michailidis E, Tu X, Palczewski K, Ong YT, Li Z, Griffin DT, Schuckmann MM, Tanuma J, Oka S, Singh K, Kodama EN, Sarafianos SG.
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Journal Title
J Biol Chem.
Volume: 287
Issue: 35
Pages: 29988-29999
DOI
Related Report
Peer Reviewed
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[Journal Article] Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant.2012
Author(s)
Michailidis E, Singh K, Ryan EM, Hachiya A, Ong YT, Kirby KA, Marchand B, Kodama EN, Mitsuya H, Parniak MA, Sarafianos SG
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Journal Title
Cell Mol Biol (Noisy-le-grand).
Volume: 58
Pages: 187-195
Related Report
Peer Reviewed
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[Presentation] Effects of natural variability of Vpr on immunological footprints and protein functions.2015
Author(s)
Kamori D, Murakami T, Hasan Z, Meribe S, Carlson J, Siarot L, Miura T, Kawana-Tachikawa A, Iwamoto A, Gatanaga H, Oka S, Aida Y, Ueno T.
Organizer
Keystone Symposia HIV Vaccines (X5)
Place of Presentation
バンフ・カナダ
Year and Date
2015-03-22 – 2015-03-27
Related Report
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[Presentation] Reduced HIV-1 Nef Function in Acute/Early Individuals who become Viremic Controllers.2013
Author(s)
X. Kuang, A Le, P Mwimanzi, T Markle, R Danroth, T Ueno, T Miura, B Walker, Z Brumme, M Brockman, and the Acute HIV and International HIV Controllers study group.
Organizer
The 20th Conference on Retroviruses and Opportunistic Infections (CROI)
Place of Presentation
Atlanta, USA
Related Report
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