作者
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
发表日期
2022/8/19
期刊
Retrovirology
卷号
19
期号
1
页码范围
18
出版商
BioMed Central
简介
Background
The generation of over 69 spliced HIV-1 mRNAs from one primary transcript by alternative RNA splicing emphasizes the central role that RNA processing plays in HIV-1 replication. Control is mediated in part through the action of host SR proteins whose activity is regulated by multiple SR kinases (CLK1-4, SRPKs).
Methods
Both shRNA depletion and small molecule inhibitors of host SR kinases were used in T cell lines and primary cells to evaluate the role of these factors in the regulation of HIV-1 gene expression. Effects on virus expression were assessed using western blotting, RT-qPCR, and immunofluorescence.
Results
The studies demonstrate that SR kinases play distinct roles; depletion of CLK1 enhanced HIV-1 gene expression, reduction of CLK2 or SRPK1 suppressed it, whereas CLK3 depletion had a modest impact. The opposing effects of CLK1 vs. CLK2 depletion were due to action at …
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S Dahal, K Clayton, T Been, R Fernet-Brochu… - Retrovirology, 2022