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Phosphorylation of the HIV-1 capsid by MELK triggers uncoating to promote viral cDNA synthesis
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نویسنده
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takeuchi h. ,saito h. ,noda t. ,miyamoto t. ,yoshinaga t. ,terahara k. ,ishii h. ,tsunetsugu-yokota y. ,yamaoka s.
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منبع
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plos pathogens - 2017 - دوره : 13 - شماره : 7
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چکیده
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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. © 2017 takeuchi et al.
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آدرس
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department of molecular virology,tokyo medical and dental university,tokyo, Japan, department of molecular virology,tokyo medical and dental university,tokyo, Japan, division of ultrastructural virology,international research center for infectious diseases,institute of medical science,the university of tokyo,tokyo,japan,presto science and technology agency,saitama,japan,laboratory of ultrastructural virology,institute for frontier life and medical sciences,kyoto university,kyoto, Japan, discovery research laboratory for core therapeutic areas,shionogi pharmaceutical research center,shionogi & co,ltd,osaka, Japan, discovery research laboratory for core therapeutic areas,shionogi pharmaceutical research center,shionogi & co,ltd,osaka, Japan, department of immunology,national institute of infectious diseases,tokyo, Japan, aids research center,national institute of infectious diseases,tokyo, Japan, department of immunology,national institute of infectious diseases,tokyo,japan,department of medical technology,tokyo university of technology,school of human sciences,tokyo, Japan, department of molecular virology,tokyo medical and dental university,tokyo, Japan
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Authors
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