2017年7月
Phosphorylation of the HIV-1 capsid by MELK triggers uncoating to promote viral cDNA synthesis.
PLoS pathogens
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- 巻
- 13
- 号
- 7
- 開始ページ
- e1006441
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1371/journal.ppat.1006441
- 出版者・発行元
- PUBLIC LIBRARY SCIENCE
Regulation of capsid disassembly is crucial for efficient HIV-1 cDNA synthesis after entry, yet host factors involved in this process remain largely unknown. Here, we employ genetic screening of human T-cells to identify maternal embryonic leucine zipper kinase (MELK) as a host factor required for optimal uncoating of the HIV-1 core to promote viral cDNA synthesis. Depletion of MELK inhibited HIV-1 cDNA synthesis with a concomitant delay of capsid disassembly. MELK phosphorylated Ser-149 of the capsid in the multimerized HIV-1 core, and a mutant virus carrying a phosphorylation-mimetic amino-acid substitution of Ser-149 underwent premature capsid disassembly and earlier HIV-1 cDNA synthesis, and eventually failed to enter the nucleus. Moreover, a small-molecule MELK inhibitor reduced the efficiency of HIV-1 replication in peripheral blood mononuclear cells in a dose-dependent manner. These results reveal a previously unrecognized mechanism of HIV-1 capsid disassembly and implicate MELK as a potential target for anti-HIV therapy.
- リンク情報
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- DOI
- https://doi.org/10.1371/journal.ppat.1006441
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/28683086
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500366
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000406623700011&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1371/journal.ppat.1006441
- ISSN : 1553-7366
- eISSN : 1553-7374
- PubMed ID : 28683086
- PubMed Central 記事ID : PMC5500366
- Web of Science ID : WOS:000406623700011