Opposing roles of CLK SR kinases in controlling HIV-1 gene expression and latency
Plain Language Summary Identifying cellular factors that regulate HIV-1 RNA processing provides important insights into novel strategies to control this infection. Different members of the SR kinase family have distinct roles in regulating virus expression because they affect distinct steps of trans...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-08-01
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| Series: | Retrovirology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12977-022-00605-4 |
| _version_ | 1798038811644526592 |
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| author | Subha Dahal Kiera Clayton Terek Been Raphaële Fernet-Brochu Alonso Villasmil Ocando Ahalya Balachandran Mikaël Poirier Rebecca Kaddis Maldonado Lulzim Shkreta Kayluz Frias Boligan Furkan Guvenc Fariha Rahman Donald Branch Brendan Bell Benoit Chabot Scott D. Gray-Owen Leslie J. Parent Alan Cochrane |
| author_facet | Subha Dahal Kiera Clayton Terek Been Raphaële Fernet-Brochu Alonso Villasmil Ocando Ahalya Balachandran Mikaël Poirier Rebecca Kaddis Maldonado Lulzim Shkreta Kayluz Frias Boligan Furkan Guvenc Fariha Rahman Donald Branch Brendan Bell Benoit Chabot Scott D. Gray-Owen Leslie J. Parent Alan Cochrane |
| author_sort | Subha Dahal |
| collection | DOAJ |
| description | Plain Language Summary Identifying cellular factors that regulate HIV-1 RNA processing provides important insights into novel strategies to control this infection. Different members of the SR kinase family have distinct roles in regulating virus expression because they affect distinct steps of transcription/RNA processing. We identify inhibitors of these kinases that suppress HIV-1 gene expression and replication in multiple assay systems at nanomolar concentrations with limited or no cytotoxicity. Our results highlight the therapeutic potential of targeting the post-integration stage of the HIV-1 lifecycle to selectively enhance or reverse provirus latency. A greater understanding of the molecular mechanisms underlying the effects observed will facilitate the development of more targeted approaches to modulate HIV-1 latency on the path toward a “functional” cure for this infection. |
| first_indexed | 2024-04-11T21:45:27Z |
| format | Article |
| id | doaj.art-f6c59f5364bf49b0a2fb808840fdf7ed |
| institution | Directory Open Access Journal |
| issn | 1742-4690 |
| language | English |
| last_indexed | 2024-04-11T21:45:27Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Retrovirology |
| spelling | doaj.art-f6c59f5364bf49b0a2fb808840fdf7ed2022-12-22T04:01:27ZengBMCRetrovirology1742-46902022-08-0119112510.1186/s12977-022-00605-4Opposing roles of CLK SR kinases in controlling HIV-1 gene expression and latencySubha Dahal0Kiera Clayton1Terek Been2Raphaële Fernet-Brochu3Alonso Villasmil Ocando4Ahalya Balachandran5Mikaël Poirier6Rebecca Kaddis Maldonado7Lulzim Shkreta8Kayluz Frias Boligan9Furkan Guvenc10Fariha Rahman11Donald Branch12Brendan Bell13Benoit Chabot14Scott D. Gray-Owen15Leslie J. Parent16Alan Cochrane17Dept. of Molecular Genetics, University of TorontoDepartment of Pathology, University of Massachusetts Medical SchoolDept. of Molecular Genetics, University of TorontoDept. of Molecular Genetics, University of TorontoRagon Institute of MGH, MIT and HarvardDept. of Molecular Genetics, University of TorontoDept. of Microbiology & Infectious Diseases, Université de SherbrookeDepartment of Medicine, Penn State College of MedicineDept. of Microbiology & Infectious Diseases, Université de SherbrookeCenter for Innovation, Canadian Blood ServicesDept. of Molecular Genetics, University of TorontoDept. of Molecular Genetics, University of TorontoCenter for Innovation, Canadian Blood ServicesDept. of Microbiology & Infectious Diseases, Université de SherbrookeDept. of Microbiology & Infectious Diseases, Université de SherbrookeDept. of Molecular Genetics, University of TorontoDepartment of Medicine, Penn State College of MedicineDept. of Molecular Genetics, University of TorontoPlain Language Summary Identifying cellular factors that regulate HIV-1 RNA processing provides important insights into novel strategies to control this infection. Different members of the SR kinase family have distinct roles in regulating virus expression because they affect distinct steps of transcription/RNA processing. We identify inhibitors of these kinases that suppress HIV-1 gene expression and replication in multiple assay systems at nanomolar concentrations with limited or no cytotoxicity. Our results highlight the therapeutic potential of targeting the post-integration stage of the HIV-1 lifecycle to selectively enhance or reverse provirus latency. A greater understanding of the molecular mechanisms underlying the effects observed will facilitate the development of more targeted approaches to modulate HIV-1 latency on the path toward a “functional” cure for this infection.https://doi.org/10.1186/s12977-022-00605-4HIV-1RNA processingSR kinasesLatency |
| spellingShingle | Subha Dahal Kiera Clayton Terek Been Raphaële Fernet-Brochu Alonso Villasmil Ocando Ahalya Balachandran Mikaël Poirier Rebecca Kaddis Maldonado Lulzim Shkreta Kayluz Frias Boligan Furkan Guvenc Fariha Rahman Donald Branch Brendan Bell Benoit Chabot Scott D. Gray-Owen Leslie J. Parent Alan Cochrane Opposing roles of CLK SR kinases in controlling HIV-1 gene expression and latency Retrovirology HIV-1 RNA processing SR kinases Latency |
| title | Opposing roles of CLK SR kinases in controlling HIV-1 gene expression and latency |
| title_full | Opposing roles of CLK SR kinases in controlling HIV-1 gene expression and latency |
| title_fullStr | Opposing roles of CLK SR kinases in controlling HIV-1 gene expression and latency |
| title_full_unstemmed | Opposing roles of CLK SR kinases in controlling HIV-1 gene expression and latency |
| title_short | Opposing roles of CLK SR kinases in controlling HIV-1 gene expression and latency |
| title_sort | opposing roles of clk sr kinases in controlling hiv 1 gene expression and latency |
| topic | HIV-1 RNA processing SR kinases Latency |
| url | https://doi.org/10.1186/s12977-022-00605-4 |
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