論文

査読有り 国際誌
2017年7月

Phosphorylation of the HIV-1 capsid by MELK triggers uncoating to promote viral cDNA synthesis.

PLoS pathogens
  • Hiroaki Takeuchi
  • ,
  • Hideki Saito
  • ,
  • Takeshi Noda
  • ,
  • Tadashi Miyamoto
  • ,
  • Tomokazu Yoshinaga
  • ,
  • Kazutaka Terahara
  • ,
  • Hiroshi Ishii
  • ,
  • Yasuko Tsunetsugu-Yokota
  • ,
  • Shoji Yamaoka

13
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
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
  • 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

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