Elucidation of molecular mechanism of HIV cell-to-cell transmission
| Project/Area Number |
16H05198
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Yokohama City University |
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Principal Investigator |
Ryo Akihide 横浜市立大学, 医学研究科, 教授 (20363814)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
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| Keywords | HIV / 宿主因子 / 細胞-細胞間感染 / プロテオミクス / 分子イメージング / ウイルス / 感染症 / 蛋白質 / プロテオーム / 微生物 / 細胞－細胞間感染 / 微生物学 |
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| Outline of Final Research Achievements |
It is widely believed that cell-to-cell viral transfer is a major mode of HIV-1 infection in lymphoid tissues and much more efficient for spreading viral particles than cell-free infection. In our present study, we created a HIV-1 molecular clone carrying 24 repeats of the MS2-binding sites in order to monitor the intracellular dynamics of Gag and vRNA in cells. Using this system, we show that the tumor suppressor adenomatous polyposis coli protein (APC) directs the localization and assembly of HIV-1 Gag polyprotein at distinct membrane components to enable the efficient production and spread of infectious viral particles. Furthermore, we newly identified anti-viral host factors that selectively suppress the cell-to-cell transmission of HIV-1.
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| Academic Significance and Societal Importance of the Research Achievements |
細胞間接触により感染細胞から非感染細胞に直接エイズウイルスを受け渡すcell-to-cell感染は通常の感染系の数十倍～数千倍という高効率なウイルス伝播が可能であり、新たな創薬ターゲットであると考えられる。本研究で見いだしたAPCはウイルス構成因子を細胞の特定の場所に集積させることで、HIVのcell-to-cell伝播を制御する宿主因子である。APCの本来の機能を阻害させないで、APCとGagの相互作用を阻止できれば、HIVの効率的な細胞-細胞間伝播が阻止できる可能性がある。ウイルス-宿主間相互作用を抑制する新しいタイプの治療薬開発へ展開が期待される。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Mutations in genes encoding polycomb repressive complex 2 subunits cause Weaver syndrome2017
Author(s)
Eri Imagawa, Ken Higashimoto, Yasunari Sakai, Chikahiko Numakura, Nobuhiko Okamoto, Satoko Matsunaga, Akihide Ryo, Yoshinori Sato, Masafumi Sanefuji, Kenji Ihara, Yui Takada, Gen Nishimura, Hirotomo Saitsu, Takeshi Mizuguchi, Satoko Miyatake, Mitsuko Nakashima, Noriko Miyake, Hidenobu Soejima, Naomichi Matsumoto
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Journal Title
Human Mutation
Volume: 印刷中
Issue: 6
Pages: 637-648
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] The tumour suppressor APC promotes HIV-1 assembly via interaction with Gag precursor protein.2017
Author(s)
Miyakawa K, Nishi M, Matsunaga S, Okayama A, Anraku M, Kudoh A, Hirano H, Kimura H, Morikawa Y, Yamamoto N, Ono A, Ryo A.
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Journal Title
Nature Communications
Volume: 8
Issue: 1
Pages: 14259-14259
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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