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Journal article
Role of Bruton's tyrosine kinase inhibitors in HIV-1-infected cells
Journal of neurovirology, v 21(3), pp 257-275
01 Jun 2015
PMID: 25672887
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Many cellular cofactors have been documented to be critical for various stages of viral replication. Using high-throughput proteomic assays, we have previously identified Bruton's tyrosine kinase (BTK) as a host protein that was uniquely upregulated in the plasma membrane of human immunodeficiency virus (HIV-1)-infected T cells. Here, we have further characterized the BTK expression in HIV-1 infection and show that this cellular factor is specifically expressed in infected myeloid cells. Significant upregulation of the phosphorylated form of BTK was observed in infected cells. Using size exclusion chromatography, we found BTK to be virtually absent in the uninfected U937 cells; however, new BTK protein complexes were identified and distributed in both high molecular weight (similar to 600 kDa) and a small molecular weight complex (similar to 60-120 kDa) in the infected U1 cells. BTK levels were highest in cells either chronically expressing virus or induced/infected myeloid cells and that BTK translocated to the membrane following induction of the infected cells. BTK knockdown in HIV-1-infected cells using small interfering RNA (siRNA) resulted in selective death of infected, but not uninfected, cells. Using BTK-specific antibody and small-molecule inhibitors including LFM-A13 and a FDA-approved compound, ibrutinib (PCI-32765), we have found that HIV-1-infected cells are sensitive to apoptotic cell death and result in a decrease in virus production. Overall, our data suggests that HIV-1-infected cells are sensitive to treatments targeting BTK expressed in infected cells.
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Details
- Title
- Role of Bruton's tyrosine kinase inhibitors in HIV-1-infected cells
- Creators
- Irene Guendel - George Mason UniversitySergey Iordanskiy - George Mason UniversityGavin C. Sampey - George Mason UniversityRachel Van Duyne - National Institutes of HealthValerie Calvert - George Mason UniversityEmanuel Petricoin - George Mason UniversityMohammed Saifuddin - WuXi AppTecKylene Kehn-Hall - George Mason UniversityFatah Kashanchi - George Mason University
- Publication Details
- Journal of neurovirology, v 21(3), pp 257-275
- Publisher
- Springer Nature
- Number of pages
- 19
- Grant note
- R21AI061560 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) AI070740; AI043894; AI11340; AI114490 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Virginia's Commonwealth Health Research Board
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000354448000007
- Scopus ID
- 2-s2.0-84939942492
- Other Identifier
- 991021903312404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences
- Virology