Molecular mechanism for polarized trafficking and budding of HIV in infectious synapses
| Project/Area Number |
16K08818
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Kitasato University |
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Principal Investigator |
Morikawa Yuko 北里大学, 感染制御科学府, 教授 (20191017)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | HIV / Gag / 輸送 / 感染シナプス / サイトカイン / 細胞骨格系 / 感染症 / ウイルス学 / 免疫学 |
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| Outline of Final Research Achievements |
HIV infected cells form an adhesive structure with target cells, termed infectious synapse, leading to efficient transmission of HIV. The present study showed that HIV uses Qc-SNARE (Syntaxin, SNAP)-mediated secretion pathways for cytokines (e.g., TNF, IL-2) in immunological synapse for intracellular trafficking of HIV Gag protein. These results may explain suppressive immune responses in HIV infected cells. The study revealed that Gag and Syntaxin were cotransported and suggested that they were transiently interacted with clathrin adapters (APs) and an ESCRT-I molecule TSG101 during the transport pathways.
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| Academic Significance and Societal Importance of the Research Achievements |
免疫細胞は抗原提示細胞と免疫シナプスと呼ばれる接着構造を形成し、サイトカインを分泌して免疫応答を誘導する。HIVはTリンパ球に感染して免疫機能不全をおこすが、HIV感染Tリンパ球は非感染Tリンパ球と接触すると、シナプス様の接着構造を形成してHIVを伝播する。本研究では、Tリンパ球におけるサイトカイン分泌経路を利用してHIV Gag蛋白が細胞内輸送されることを示唆した。この結果はHIV感染による免疫応答抑制を説明しうる。また、Gag蛋白がサイトカイン分泌に関与する分子により輸送される過程で、様々な宿主因子と相互作用する可能性を示唆した。
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Report
(4 results)
Research Products
(14 results)
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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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