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  A molecular tweezer antagonizes seminal amyloids and HIV infection

Lump, E., Castellano, L. M., Meier, C., Seeliger, J., Erwin, N., Sperlich, B., Stürzel, C. M., Usmani, S., Hammond, R. M., von Einem, J., Gerold, G., Kreppel, F., Bravo-Rodriguez, K., Pietschmann, T., Holmes, V. M., Palesch, D., Zirafi, O., Weissman, D., Sowislok, A., Kirchhoff, F., Weil, T., Klärner, F.-G., Schrader, T., Bitan, G., Sanchez-Garcia, E., Winter, R., Shorter, J., & Münch, J. (2015). A molecular tweezer antagonizes seminal amyloids and HIV infection. eLife,. doi:10.7554/eLife.05397.

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アイテムのパーマリンク: https://hdl.handle.net/11858/00-001M-0000-0028-3ED7-8 版のパーマリンク: https://hdl.handle.net/11858/00-001M-0000-002A-21B3-3
資料種別: 学術論文

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作成者

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 作成者:
Lump, Edina1, 著者
Castellano, Laura M.2, 3, 著者
Meier, Christoph4, 著者
Seeliger, Janine5, 著者
Erwin, Nelli5, 著者
Sperlich, Benjamin5, 著者
Stürzel, Christina M.1, 著者
Usmani, Shariq1, 著者
Hammond, Rebecca M.2, 6, 著者
von Einem, Jens7, 著者
Gerold, Gisa8, 著者
Kreppel, Florian9, 著者
Bravo-Rodriguez, Kenny10, 著者           
Pietschmann, Thomas8, 著者
Holmes, Veronica M.11, 著者
Palesch, David1, 著者
Zirafi, Onofrio 1, 著者
Weissman, Drew11, 著者
Sowislok, Andrea 12, 著者
Kirchhoff, Frank1, 13, 著者
Weil, Tanja4, 13, 著者Klärner, Frank-Gerrit14, 著者Schrader, Thomas12, 著者Bitan, Gal15, 16, 17, 著者Sanchez-Garcia, Elsa10, 著者           Winter, Roland5, 著者Shorter, James2, 3, 著者Münch, Jan1, 13, 著者 全て表示
所属:
1Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany, ou_persistent22              
2Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States;, ou_persistent22              
3Pharmacology Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States, ou_persistent22              
4Institute of Organic Chemistry III/Macromolecular Chemistry, Ulm University, Ulm, Germany, ou_persistent22              
5Physical Chemistry I—Biophysical Chemistry, Department of Chemistry and Chemical Biology, Technical University of Dortmund, Dortmund, Germany, ou_persistent22              
6Biology Department, Swarthmore College, Swarthmore, United States, ou_persistent22              
7Institute of Virology, Ulm University Medical Center, Ulm, Germany, ou_persistent22              
8Institute of Experimental Virology, Twincore, Centre for Experimental and Clinical Infection Research, Hannover, Germany, ou_persistent22              
9Institute of Gene Therapy, Ulm University Medical Center, Ulm, Germany, ou_persistent22              
10Research Group Sánchez-García, Max-Planck-Institut für Kohlenforschung, Max Planck Society, ou_1950289              
11Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States, ou_persistent22              
12Department of Chemistry, University of Duisburg-Essen, Essen, Germany, ou_persistent22              
13Ulm-Peptide Pharmaceuticals, Ulm University, Ulm, Germany, ou_persistent22              
14Institute of Organic Chemistry, University of Duisburg-Essen, Essen, Germany, ou_persistent22              
15Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States, ou_persistent22              
16Brain Research Institute, University of California at Los Angeles, Los Angeles, Los Angeles, United States, ou_persistent22              
17Molecular Biology Institute, University of California, Los Angeles, United States, ou_persistent22              

内容説明

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キーワード: -
 要旨: Semen is the main vector for HIV transmission and contains amyloid fibrils that enhance viral infection. Available microbicides that target viral components have proven largely ineffective in preventing sexual virus transmission. In this study, we establish that CLR01, a ‘molecular tweezer’ specific for lysine and arginine residues, inhibits the formation of infectivity-enhancing seminal amyloids and remodels preformed fibrils. Moreover, CLR01 abrogates semen-mediated enhancement of viral infection by preventing the formation of virion–amyloid complexes and by directly disrupting the membrane integrity of HIV and other enveloped viruses. We establish that CLR01 acts by binding to the target lysine and arginine residues rather than by a non-specific, colloidal mechanism. CLR01 counteracts both host factors that may be important for HIV transmission and the pathogen itself. These combined anti-amyloid and antiviral activities make CLR01 a promising topical microbicide for blocking infection by HIV and other sexually transmitted viruses.

資料詳細

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言語: eng - English
 日付: 2014-10-302015-07-202015-08-18
 出版の状態: オンラインで出版済み
 ページ: 33
 出版情報: -
 目次: -
 査読: 査読あり
 識別子（DOI, ISBNなど）: DOI: 10.7554/eLife.05397
 学位: -

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出版物 1

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出版物名: eLife
種別: 学術雑誌
 著者・編者:
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出版社, 出版地: Cambridge, UK : eLife Sciences Publications, Ltd
ページ: - 巻号: - 通巻号: 4:e05397 開始・終了ページ: - 識別子（ISBN, ISSN, DOIなど）: ISSN: 2050-084X