دورية أكاديمية
أعرض في EDS

Low-Level Ionizing Radiation Induces Selective Killing of HIV-1-Infected Cells with Reversal of Cytokine Induction Using mTOR Inhibitors.

التفاصيل البيبلوغرافية
العنوان: Low-Level Ionizing Radiation Induces Selective Killing of HIV-1-Infected Cells with Reversal of Cytokine Induction Using mTOR Inhibitors.
المؤلفون: Pinto DO; Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA., DeMarino C; Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA., Vo TT; Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA., Cowen M; Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA., Kim Y; Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA., Pleet ML; Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA., Barclay RA; Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA., Noren Hooten N; Laboratory of Epidemiology and Population Science, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA., Evans MK; Laboratory of Epidemiology and Population Science, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA., Heredia A; Institute of Human Virology, University of Maryland School of Medicine, University of Maryland, Baltimore, MD 21201, USA., Batrakova EV; Department of Medicine, University of North Carolina HIV Cure Center; University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA., Iordanskiy S; Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA., Kashanchi F; Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA.
المصدر: Viruses [Viruses] 2020 Aug 13; Vol. 12 (8). Date of Electronic Publication: 2020 Aug 13.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مواضيع طبية MeSH: Radiation, Ionizing*, Cytokines/*immunology , Extracellular Vesicles/*immunology , HIV-1/*radiation effects , TOR Serine-Threonine Kinases/*antagonists & inhibitors , Virus Latency/*drug effects, Antiviral Agents/pharmacology ; Autophagy/drug effects ; Benzoxazoles/pharmacology ; CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/radiation effects ; CD4-Positive T-Lymphocytes/virology ; Extracellular Vesicles/virology ; Female ; HIV-1/drug effects ; Humans ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/virology ; Male ; Myeloid Cells/drug effects ; Myeloid Cells/radiation effects ; Myeloid Cells/virology ; Pyrimidines/pharmacology ; Sirolimus/pharmacology ; U937 Cells ; Virus Activation/radiation effects
مستخلص: HIV-1 infects 39.5 million people worldwide, and cART is effective in preventing viral spread by reducing HIV-1 plasma viral loads to undetectable levels. However, viral reservoirs persist by mechanisms, including the inhibition of autophagy by HIV-1 proteins (i.e., Nef and Tat). HIV-1 reservoirs can be targeted by the "shock and kill" strategy, which utilizes latency-reversing agents (LRAs) to activate latent proviruses and immunotarget the virus-producing cells. Yet, limitations include reduced LRA permeability across anatomical barriers and immune hyper-activation. Ionizing radiation (IR) induces effective viral activation across anatomical barriers. Like other LRAs, IR may cause inflammation and modulate the secretion of extracellular vesicles (EVs). We and others have shown that cells may secrete cytokines and viral proteins in EVs and, therefore, LRAs may contribute to inflammatory EVs. In the present study, we mitigated the effects of IR-induced inflammatory EVs (i.e., TNF-α), through the use of mTOR inhibitors (mTORi; Rapamycin and INK128). Further, mTORi were found to enhance the selective killing of HIV-1-infected myeloid and T-cell reservoirs at the exclusion of uninfected cells, potentially via inhibition of viral transcription/translation and induction of autophagy. Collectively, the proposed regimen using cART, IR, and mTORi presents a novel approach allowing for the targeting of viral reservoirs, prevention of immune hyper-activation, and selectively killing latently infected HIV-1 cells.
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فهرسة مساهمة: Keywords: HIV-1; HIV-1 therapy; Ionizing radiation; autophagy; cell death; extracellular vesicles; inflammation; latency reversal; mTOR inhibition; shock and kill
المشرفين على المادة: 0 (Antiviral Agents)
0 (Benzoxazoles)
0 (Cytokines)
0 (Pyrimidines)
EC 2.7.1.1 (MTOR protein, human)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
JGH0DF1U03 (sapanisertib)
W36ZG6FT64 (Sirolimus)
تواريخ الأحداث: Date Created: 20200823 Date Completed: 20210224 Latest Revision: 20240801
رمز التحديث: 20240801
مُعرف محوري في PubMed: PMC7472203
DOI: 10.3390/v12080885
PMID: 32823598
قاعدة البيانات: MEDLINE
الوصف
تدمد:1999-4915
DOI:10.3390/v12080885