Kinase control of latent HIV-1 infection: PIM-1 kinase as a major contributor to HIV-1 reactivation

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Publication Type pre-print
School or College School of Medicine
Department Pathology
Creator Planelles, Vicente
Other Author Duverger, Alexandra; Wolschendorf, Frank; Anderson, Joshua C.; Wagner, Frederic; Bosque, Alberto; Shishido, Takao; Jones, Jennifer; Willey, Christopher; Cron, Randall Q.; Kutsch, Olaf
Title Kinase control of latent HIV-1 infection: PIM-1 kinase as a major contributor to HIV-1 reactivation
Date 2014-01-01
Description Despite the clinical relevance of latent HIV-1 infection as a block to HIV-1 eradication, the molecular biology of HIV-1 latency remains incompletely understood. We recently demonstrated the presence of a gatekeeper kinase function that controls latent HIV-1 infection. Using kinase array analysis we here expand on this finding and demonstrate that the kinase activity profile of latently HIV-1 infected T cells is altered relative to uninfected T cells. A ranking of altered kinases generated from these kinome profile data predicted PIM-1 kinase as a key switch involved in HIV-1 latency control. Using genetic and pharmacologic perturbation strategies, we demonstrate that PIM-1 activity is indeed required for HIV-1 reactivation in T cell lines and primary CD4 T cells. The presented results thus confirm that kinases are key contributors to HIV-1 latency control. In addition, through mutational studies we link the inhibitory effect of PIM-1 inhibitor IV (PIMi IV) on HIV-1 reactivation to an AP-1 motif in the CD28 responsive element of the HIV-1 long terminal repeat (LTR). The results expand our conceptual understanding of the dynamic interactions of the host-cell and the latent HIV-1 integration event and position kinome profiling as a research tool to reveal novel molecular mechanisms that can eventually be targeted to therapeutically trigger HIV-1 reactivation.
Type Text
Publisher American Society for Microbiology
Volume 88
Issue 1
First Page 364
Last Page 376
Language eng
Bibliographic Citation Duverger, A., Wolschendorf, F., Anderson, J. C., Wagner, F., Bosque, A., Shishido, T., Jones, J., Planelles, V., Willey, C., Cron, R. Q., & Kutsch, O. (2014). Kinase control of latent HIV-1 infection: PIM-1 kinase as a major contributor to HIV-1 reactivation. Journal of Virology, 88(1), 364-76.
Rights Management (c)American Society for Microbiology ; doi: 10.1128/JVI.02682-13
Format Medium application/pdf
Format Extent 4,925,307 bytes
Identifier uspace,18425
ARK ark:/87278/s6808br1
Setname ir_uspace
Date Created 2014-04-25
Date Modified 2014-04-28
ID 712506
Reference URL https://collections.lib.utah.edu/ark:/87278/s6808br1
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