ArticlePLoS pathogens2017
Phosphorylation of the HIV-1 capsid by MELK triggers uncoating to promote viral cDNA synthesis.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- BRCA1-RAD51 homologous DNA repair pathway promotes HIV-1 reverse transcription.Science advances · 2026Article
- Review
- Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication.FEMS microbiology reviews · 2026Review
- Screening kinase inhibitors identifies MELK as a prime target against influenza virus infections through inhibition of viral mRNA splicing.Frontiers in microbiology · 2025Article
- Capsid-host interactions for HIV-1 ingress.Microbiology and molecular biology reviews : MMBR · 2023Review
- Adaptive learning embedding features to improve the predictive performance of SARS-CoV-2 phosphorylation sites.Bioinformatics (Oxford, England) · 2023Article
- Multi-OMICs landscape of SARS-CoV-2-induced host responses in human lung epithelial cells.iScience · 2023Article
- Application of CRISPR-Cas9 Gene Editing for HIV Host Factor Discovery and Validation.Pathogens (Basel, Switzerland) · 2022Review
- Arginyl-tRNA-protein transferase 1 contributes to governing optimal stability of the human immunodeficiency virus type 1 core.Retrovirology · 2021Article
- Saccharomyces cerevisiae RNA lariat debranching enzyme, Dbr1p, is required for completion of reverse transcription by the retrovirus-like element Ty1 and cleaves branched Ty1 RNAs.Molecular genetics and genomics : MGG · 2021Article
- Structure, Function, and Interactions of the HIV-1 Capsid Protein.Life (Basel, Switzerland) · 2021Review
- HIV-1 Capsid Core: A Bullet to the Heart of the Target Cell.Frontiers in microbiology · 2021Review
- Inhibition of MELK produces potential anti-tumour effects in bladder cancer by inducing G1/S cell cycle arrest via the ATM/CHK2/p53 pathway.Journal of cellular and molecular medicine · 2020Article
- Spermidine/spermine N1-acetyltransferase 1 is a gene-specific transcriptional regulator that drives brain tumor aggressiveness.Oncogene · 2019Article
- Allosteric Regulation of HIV-1 Capsid Structure for Gag Assembly, Virion Production, and Viral Infectivity by a Disordered Interdomain Linker.Journal of virology · 2019Article
- PIM kinases facilitate lentiviral evasion from SAMHD1 restriction via Vpx phosphorylation.Nature communications · 2019Article
- Role for Gag-CA Interdomain Linker in Primate Lentiviral Replication.Frontiers in microbiology · 2019Article
- Toward the "unravelling" of HIV: Host cell factors involved in HIV-1 core uncoating.PLoS pathogens · 2018Article
- Post-translational Modification-Based Regulation of HIV Replication.Frontiers in microbiology · 2018Review
- In vitro methods for testing antiviral drugs.Biotechnology advancesReview
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.