Journal article
Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells
Virology (New York, N.Y.), v 485, pp 1-15
01 Nov 2015
PMID: 26184775
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The highly active antiretroviral therapy reduces HIV-1 RNA in plasma to undetectable levels. However, the virus continues to persist in the long-lived resting CD4+ T cells, macrophages and astrocytes which form a viral reservoir in infected individuals. Reactivation of viral transcription is critical since the host immune response in combination with antiretroviral therapy may eradicate the virus. Using the chronically HIV-1 infected T lymphoblastoid and monocytic cell lines, primary quiescent CD4+ T cells and humanized mice infected with dual-tropic HIV-1 89.6, we examined the effect of various X-ray irradiation (IR) doses (used for HIV-related lymphoma treatment and lower doses) on HIV-1 transcription and viability of infected cells. Treatment of both T cells and monocytes with IR, a well-defined stress signal, led to increase of HIV-1 transcription, as evidenced by the presence of RNA polymerase II and reduction of HDAC1 and methyl transferase SUV39H1 on the HIV-1 promoter. This correlated with the increased GFP signal and elevated level of intracellular HIV-1 RNA in the IR-treated quiescent CD4+ T cells infected with GFP-encoding HIV-1. Exposition of latently HIV-1infected monocytes treated with PKC agonist bryostatin 1 to IR enhanced transcription activation effect of this latency-reversing agent. Increased HIV-1 replication after IR correlated with higher cell death: the level of phosphorylated Ser46 in p53, responsible for apoptosis induction, was markedly higher in the HIV-1 infected cells following IR treatment. Exposure of HIV-1 infected humanized mice with undetectable viral RNA level to IR resulted in a significant increase of HIV-1 RNA in plasma, lung and brain tissues. Collectively, these data point to the use of low to moderate dose of IR alone or in combination with HIV-1 transcription activators as a potential application for the “Shock and Kill” strategy for latently HIV-1 infected cells.
•X-ray irradiation (IR) increases HIV-1 transcription in latently-infected cells.•IR enhances activating effect of bryostatin 1 on HIV-1 transcription in monocytes.•IR induces apoptosis in HIV-1 infected cells via phosphorylation of p53 Ser46.•IR of HIV-1 infected humanized mice increases HIV-1 RNA in plasma, lung and brain.
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Details
- Title
- Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells
- Creators
- Sergey Iordanskiy - George Mason UniversityRachel Van Duyne - National Cancer InstituteGavin C Sampey - George Mason UniversityCaitlin M Woodson - George Mason UniversityKelsi Fry - George Mason UniversityMohammed Saifuddin - George Mason UniversityJia Guo - George Mason UniversityYuntao Wu - George Mason UniversityFabio Romerio - University of Maryland, BaltimoreFatah Kashanchi - George Mason University
- Publication Details
- Virology (New York, N.Y.), v 485, pp 1-15
- Publisher
- Elsevier
- Number of pages
- 15
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000363993100001
- Scopus ID
- 2-s2.0-84937060496
- Other Identifier
- 991021902520904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Virology