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Phosphorylation of the HIV-1 capsid by MELK triggers uncoating to promote viral cDNA synthesis.
- Source :
-
PLoS Pathogens . 7/6/2017, Vol. 13 Issue 7, p1-35. 35p. - Publication Year :
- 2017
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PHOSPHORYLATION
*CAPSIDS
*DNA synthesis
*COMPLEMENTARY DNA
*SMALL molecules
Subjects
Details
- Language :
- English
- ISSN :
- 15537366
- Volume :
- 13
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 123944173
- Full Text :
- https://doi.org/10.1371/journal.ppat.1006441