Publications by authors named "Young-Bong Choi"

39 Publications

Diagnostic evaluation of qRT-PCR-based kit and dPCR-based kit for COVID-19.

Genes Genomics 2021 11 15;43(11):1277-1288. Epub 2021 Sep 15.

Department of Bio-Convergence Engineering, Dankook University, Jukjeon, 16890, Republic of Korea.

Background: Coronavirus disease of 2019 (COVID-19) is well known as a fatal disease, first discovered at Wuhan in China, ranging from mild to death, such as shortness of breath and fever. Early diagnosis of COVID-19 is a crucial point in preventing global prevalence.

Objective: We aimed to evaluate the diagnostic competency and efficiency with the Allplex™ 2019-nCoV Assay kit and the Dr. PCR 20 K COVID-19 Detection kit, designed based on the qRT-PCR and dPCR technologies, respectively.

Methods: A total of 30 negative and 20 COVID-19 positive specimens were assigned to the diagnostic test by using different COVID-19 diagnosis kits. Diagnostic accuracy was measured by statistical testing with sensitivity, specificity, and co-efficiency calculations.

Results: Comparing both diagnostic kits, we confirmed that the diagnostic results of 30 negative and 20 positive cases were the same pre-diagnostic results. The diagnostic statistics test results were perfectly matched with value (1). Cohen's Kappa coefficient was demonstrated that the given kits in two different ways were "almost perfect" with value (1). In evaluating the detection capability, the dilutional linearity experiments substantiate that the Dr. PCR 20 K COVID-19 Detection kit could detect SARS-CoV-2 viral load at a concentration ten times lower than that of the Allplex™ 2019-nCoV Assay kit.

Conclusions: In this study, we propose that the dPCR diagnosis using LOAA dPCR could be a powerful method for COVID-19 point-of-care tests requiring immediate diagnosis in a limited time and space through the advantages of relatively low sample concentration and small equipment size compared to conventional qRT-PCR.
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http://dx.doi.org/10.1007/s13258-021-01162-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441239PMC
November 2021

Autophagy-competent mitochondrial translation elongation factor TUFM inhibits caspase-8-mediated apoptosis.

Cell Death Differ 2021 Sep 12. Epub 2021 Sep 12.

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.

Mitochondria support multiple cell functions, but an accumulation of dysfunctional or excessive mitochondria is detrimental to cells. We previously demonstrated that a defect in the autophagic removal of mitochondria, termed mitophagy, leads to the acceleration of apoptosis induced by herpesvirus productive infection. However, the exact molecular mechanisms underlying activation of mitophagy and regulation of apoptosis remain poorly understood despite the identification of various mitophagy-associated proteins. Here, we report that the mitochondrial translation elongation factor Tu, a mitophagy-associated protein encoded by the TUFM gene, locates in part on the outer membrane of mitochondria (OMM) where it acts as an inhibitor of altered mitochondria-induced apoptosis through its autophagic function. Inducible depletion of TUFM potentiated caspase-8-mediated apoptosis in virus-infected cells with accumulation of altered mitochondria. In addition, TUFM depletion promoted caspase-8 activation induced by treatment with TNF-related apoptosis-inducing ligand in cancer cells, potentially via dysregulation of mitochondrial dynamics and mitophagy. Importantly, we revealed the existence of and structural requirements for autophagy-competent TUFM on the OMM; the GxxxG motif within the N-terminal mitochondrial targeting sequences of TUFM was required for self-dimerization and mitophagy. Furthermore, we found that autophagy-competent TUFM was subject to ubiquitin-proteasome-mediated degradation but stabilized upon mitophagy or autophagy activation. Moreover, overexpression of autophagy-competent TUFM could inhibit caspase-8 activation. These studies extend our knowledge of mitophagy regulation of apoptosis and could provide a novel strategic basis for targeted therapy of cancer and viral diseases.
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http://dx.doi.org/10.1038/s41418-021-00868-yDOI Listing
September 2021

Development of a Glucose Sensor Based on Glucose Dehydrogenase Using Polydopamine-Functionalized Nanotubes.

Membranes (Basel) 2021 May 24;11(6). Epub 2021 May 24.

Department of Chemistry, College of Science & Technology, Dankook University, Dandae-ro, Cheonan-si, Chungnam 31116, Korea.

The electrochemical-based detection of glucose is widely used for diagnostic purposes and is mediated by enzyme-mediated signal transduction mechanisms. For such applications, recent attention has focused on utilizing the oxygen-insensitive glucose dehydrogenase (GDH) enzyme in place of the glucose oxidase (GOx) enzyme, which is sensitive to oxygen levels. Currently used Ru-based redox mediators mainly work with GOx, while Ru(dmo-bpy)Cl has been proposed as a promising mediator that works with GDH. However, there remains an outstanding need to improve Ru(dmo-bpy)Cl attachment to electrode surfaces. Herein, we report the use of polydopamine-functionalized multi-walled carbon nanotubes (PDA-MWCNTs) to effectively attach Ru(dmo-bpy)Cl and GDH onto screen-printed carbon electrodes (SPCEs) without requiring a cross-linker. PDA-MWCNTs were characterized by Fourier transform infrared (FT-IR) spectroscopy, Raman spectroscopy, and thermal gravimetric analysis (TGA), while the fabrication and optimization of Ru(dmo-bpy)Cl/PDA-MWCNT/SPCEs were characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) measurements. The experimental results demonstrate a wide linear range of glucose-concentration-dependent responses and the multi-potential step (MPS) technique facilitated the selective detection of glucose in the presence of physiologically relevant interfering species, as well as in biological fluids (e.g., serum). The ease of device fabrication and high detection performance demonstrate a viable pathway to develop glucose sensors based on the GDH enzyme and Ru(dmo-bpy)Cl redox mediator and the sensing strategy is potentially extendable to other bioanalytes as well.
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http://dx.doi.org/10.3390/membranes11060384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225004PMC
May 2021

Herpesvirus Regulation of Selective Autophagy.

Viruses 2021 05 1;13(5). Epub 2021 May 1.

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

Selective autophagy has emerged as a key mechanism of quality and quantity control responsible for the autophagic degradation of specific subcellular organelles and materials. In addition, a specific type of selective autophagy (xenophagy) is also activated as a line of defense against invading intracellular pathogens, such as viruses. However, viruses have evolved strategies to counteract the host's antiviral defense and even to activate some proviral types of selective autophagy, such as mitophagy, for their successful infection and replication. This review discusses the current knowledge on the regulation of selective autophagy by human herpesviruses.
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http://dx.doi.org/10.3390/v13050820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147283PMC
May 2021

Pentacyanoammineferrate-Based Non-Enzymatic Electrochemical Biosensing Platform for Selective Uric Acid Measurement.

Sensors (Basel) 2021 Feb 24;21(5). Epub 2021 Feb 24.

Department of Chemistry, College of Natural Science, Dankook University, Anseo-Dong, Cheonan, Chungnam 31116, Korea.

The electrochemical-based detection of uric acid (UA) is widely used for diagnostic purposes. However, various interfering species such as ascorbic acid, dopamine, and glucose can affect electrochemical signals, and hence there is an outstanding need to develop improved sensing platforms to detect UA with high selectivity. Herein, we report a pentagonal mediator-based non-enzymatic electrochemical biosensing platform to selectively measure UA in the presence of interfering species. The working electrode was fabricated by electrodepositing polymerized 1-vinylimidazole (PVI), which has an imidazole ligand, onto indium tin oxide (ITO), and then conjugating nickel ions to the PVI-coated ITO electrode. Electrode performance was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) measurements and integrated together with pentacyanoammineferrate, which can bind to the amine groups of UA and function as an electron transferring mediator. The experimental results showed a wide linear range of UA concentration-dependent responses and the multi-potential step (MPS) technique facilitated selective detection of UA in the presence of physiologically relevant interfering species. Altogether, these findings support that pentacyanoammineferrate-based non-enzymatic electrodes are suitable biosensing platforms for the selective measurement of UA, and such approaches could potentially be extended to other bioanalytes as well.
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http://dx.doi.org/10.3390/s21051574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956465PMC
February 2021

The E3/E4 ubiquitin conjugation factor UBE4B interacts with and ubiquitinates the HTLV-1 Tax oncoprotein to promote NF-κB activation.

PLoS Pathog 2020 12 23;16(12):e1008504. Epub 2020 Dec 23.

Department of Microbiology and Immunology, Penn State College School of Medicine, Hershey, Pennsylvania, United States of America.

Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATLL), and the neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 Tax protein persistently activates the NF-κB pathway to enhance the proliferation and survival of HTLV-1 infected T cells. Lysine 63 (K63)-linked polyubiquitination of Tax provides an important regulatory mechanism that promotes Tax-mediated interaction with the IKK complex and activation of NF-κB; however, the host proteins regulating Tax ubiquitination are largely unknown. To identify new Tax interacting proteins that may regulate its ubiquitination we conducted a yeast two-hybrid screen using Tax as bait. This screen yielded the E3/E4 ubiquitin conjugation factor UBE4B as a novel binding partner for Tax. Here, we confirmed the interaction between Tax and UBE4B in mammalian cells by co-immunoprecipitation assays and demonstrated colocalization by proximity ligation assay and confocal microscopy. Overexpression of UBE4B specifically enhanced Tax-induced NF-κB activation, whereas knockdown of UBE4B impaired Tax-induced NF-κB activation and the induction of NF-κB target genes in T cells and ATLL cell lines. Furthermore, depletion of UBE4B with shRNA resulted in apoptotic cell death and diminished the proliferation of ATLL cell lines. Finally, overexpression of UBE4B enhanced Tax polyubiquitination, and knockdown or CRISPR/Cas9-mediated knockout of UBE4B attenuated both K48- and K63-linked polyubiquitination of Tax. Collectively, these results implicate UBE4B in HTLV-1 Tax polyubiquitination and downstream NF-κB activation.
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http://dx.doi.org/10.1371/journal.ppat.1008504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790423PMC
December 2020

Novel Functions and Virus-Host Interactions Implicated in Pathogenesis and Replication of Human Herpesvirus 8.

Recent Results Cancer Res 2021 ;217:245-301

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, 1650 Orleans Street, Baltimore, MD, 21287, USA.

Human herpesvirus 8 (HHV-8) is classified as a γ2-herpesvirus and is related to Epstein-Barr virus (EBV), a γ1-herpesvirus. One important aspect of the γ-herpesviruses is their association with neoplasia, either naturally or in animal model systems. HHV-8 is associated with B-cell-derived primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD), endothelial-derived Kaposi's sarcoma (KS), and KSHV inflammatory cytokine syndrome (KICS). EBV is also associated with a number of B-cell malignancies, such as Burkitt's lymphoma, Hodgkin's lymphoma, and posttransplant lymphoproliferative disease, in addition to epithelial nasopharyngeal and gastric carcinomas. Despite the similarities between these viruses and their associated malignancies, the particular protein functions and activities involved in key aspects of virus biology and neoplastic transformation appear to be quite distinct. Indeed, HHV-8 specifies a number of proteins for which counterparts had not previously been identified in EBV, other herpesviruses, or even viruses in general, and these proteins are believed to play vital functions in virus biology and to be involved centrally in viral pathogenesis. Additionally, a set of microRNAs encoded by HHV-8 appears to modulate the expression of multiple host proteins to provide conditions conductive to virus persistence within the host and possibly contributing to HHV-8-induced neoplasia. Here, we review the molecular biology underlying these novel virus-host interactions and their potential roles in both virus biology and virus-associated disease.
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http://dx.doi.org/10.1007/978-3-030-57362-1_11DOI Listing
January 2021

Two-Ply Carbon Nanotube Fiber-Typed Enzymatic Biofuel Cell Implanted in Mice.

IEEE Trans Nanobioscience 2020 07;19(3):333-338

Implantable devices have emerged as a promising industry. It is inevitable that these devices will require a power source to operate in vivo. Thus, to power implantable medical devices, biofuel cells (BFCs) that generate electricity using glucose without an external power supply have been considered. Although implantable BFCs have been developed for application in vivo, they are limited by their bulky electrodes and low power density. In the present study, we attempted to apply to living mice an implantable enzymatic BFC (EBFC) that was previously reported to be a high-power EBFC comprising carbon nanotube yarn electrodes. To improve their mechanical properties and for convenient implantation, the electrodes were coated with Nafion and twisted into a micro-sized, two-ply, one-body system. When the two-ply EBFC system was implanted in the abdominal cavity of mice, it provided a high-power density of 0.3 mW/cm. The two-ply EBFC system was injected through a needle using a syringe without surgery and the inflammatory response in vivo initially induced by the injection of the EBFC system was attenuated after 7 days, indicating the biocompatibility of the system in vivo.
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http://dx.doi.org/10.1109/TNB.2020.2995143DOI Listing
July 2020

Author Correction: Performance of a glucose-reactive enzyme-based biofuel cell system for biomedical applications.

Sci Rep 2019 Nov 27;9(1):18044. Epub 2019 Nov 27.

Department of Chemistry, College of Natural Science, Dankook University, Chungnam, Cheonan, 31116, Republic of Korea.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-019-54377-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879505PMC
November 2019

Performance of a glucose-reactive enzyme-based biofuel cell system for biomedical applications.

Sci Rep 2019 07 26;9(1):10872. Epub 2019 Jul 26.

Department of Chemistry, College of Natural Science, Dankook University, Chungnam, Cheonan, 31116, Republic of Korea.

A glucose-reactive enzyme-based biofuel cell system (EBFC) was recently introduced in the scientific community for biomedical applications, such as implantable artificial organs and biosensors for drug delivery. Upon direct contact with tissues or organs, an implanted EBFC can exert effects that damage or stimulate intact tissue due to its byproducts or generated electrical cues, which have not been investigated in detail. Here, we perform a fundamental cell culture study using a glucose dehydrogenase (GDH) as an anode enzyme and bilirubin oxidase (BOD) as a cathode enzyme. The fabricated EBFC had power densities of 15.26 to 38.33 nW/cm depending on the enzyme concentration in media supplemented with 25 mM glucose. Despite the low power density, the GDH-based EBFC showed increases in cell viability (~150%) and cell migration (~90%) with a relatively low inflammatory response. However, glucose oxidase (GOD), which has been used as an EBFC anode enzyme, revealed extreme cytotoxicity (~10%) due to the lethal concentration of HO byproducts (~1500 µM). Therefore, with its cytocompatibility and cell-stimulating effects, the GDH-based EBFC is considered a promising implantable tool for generating electricity for biomedical applications. Finally, the GDH-based EBFC can be used for introducing electricity during cell culture and the fabrication of organs on a chip and a power source for implantable devices such as biosensors, biopatches, and artificial organs.
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http://dx.doi.org/10.1038/s41598-019-47392-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659637PMC
July 2019

Activation of NIX-mediated mitophagy by an interferon regulatory factor homologue of human herpesvirus.

Nat Commun 2019 07 19;10(1):3203. Epub 2019 Jul 19.

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.

Viral control of mitochondrial quality and content has emerged as an important mechanism for counteracting the host response to virus infection. Despite the knowledge of this crucial function of some viruses, little is known about how herpesviruses regulate mitochondrial homeostasis during infection. Human herpesvirus 8 (HHV-8) is an oncogenic virus causally related to AIDS-associated malignancies. Here, we show that HHV-8-encoded viral interferon regulatory factor 1 (vIRF-1) promotes mitochondrial clearance by activating mitophagy to support virus replication. Genetic interference with vIRF-1 expression or targeting to the mitochondria inhibits HHV-8 replication-induced mitophagy and leads to an accumulation of mitochondria. Moreover, vIRF-1 binds directly to a mitophagy receptor, NIX, on the mitochondria and activates NIX-mediated mitophagy to promote mitochondrial clearance. Genetic and pharmacological interruption of vIRF-1/NIX-activated mitophagy inhibits HHV-8 productive replication. Our findings uncover an essential role of vIRF-1 in mitophagy activation and promotion of HHV-8 lytic replication via this mechanism.
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http://dx.doi.org/10.1038/s41467-019-11164-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642096PMC
July 2019

Stretchable Fiber Biofuel Cell by Rewrapping Multiwalled Carbon Nanotube Sheets.

Nano Lett 2018 08 16;18(8):5272-5278. Epub 2018 Jul 16.

Center for Self-Powered Actuation, Department of Biomedical Engineering , Hanyang University , Seoul 04763 , Korea.

The fiber-type biofuel cell is attractive as an implantable energy source because the fiber can modify various structures and the wound can be stitched like a suture. In addition, in daily life, the biofuel cell is forced by human motion, and stretchability is a critical requirement for real applications. Therefore, we introduce a new type of highly stretchable, stable, soft fiber biofuel cell with microdiameter dimensions as an energy harvester. The completed biofuel cell operated well in fluids similar to human fluids, such as 20 mM phosphate-buffered 0.14 M NaCl solution (39.5 mW/cm) and human serum (36.6 μW/cm). The fiber-type biofuel cell can be reversibly stretched up to 100% in tensile direction while producing sustainable electrical power. In addition, the unique rewrapping structure, which traps the enzyme between multiwalled carbon nanotube sheets, enormously enhanced the stability of the biofuel cell when the biofuel cell was repeatedly stretched (the power density retention increased from 63 to 99%) and operated in human serum (the power density retention increased from 29 to 86%). The fiber can be easily woven into various structures, such as McKibben braid yarn, and scaled up by series and parallel connections.
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http://dx.doi.org/10.1021/acs.nanolett.8b02256DOI Listing
August 2018

Peroxisomes support human herpesvirus 8 latency by stabilizing the viral oncogenic protein vFLIP via the MAVS-TRAF complex.

PLoS Pathog 2018 05 10;14(5):e1007058. Epub 2018 May 10.

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.

Human herpesvirus 8 (HHV-8) is causally related to human malignancies. HHV-8 latent viral FLICE-inhibitory protein (vFLIP) is a viral oncoprotein that is linked to pathogenesis, but how its expression is regulated is largely unknown. In an attempt to understand the role of the mitochondrial antiviral signaling (MAVS) adaptor in HHV-8 infection, we discovered that vFLIP expression was post-translationally up-regulated by the MAVS signaling complex on peroxisomes. Furthermore, we demonstrated that vFLIP could be targeted to the peroxisomes, where it was oncogenically active, in a PEX19-dependent manner. Targeted disruption of vFLIP and MAVS interaction resulted in a decrease in vFLIP expression and selectively promoted death of latently HHV-8-infected cells, providing therapeutic potential for treating HHV-8 diseases. Collectively, our experimental results suggest novel involvement of peroxisomes and MAVS in the stabilization of vFLIP and thereby in the establishment or maintenance of HHV-8 latency and associated pathogenesis.
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http://dx.doi.org/10.1371/journal.ppat.1007058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963799PMC
May 2018

Ultrasonic synthesis and characterization of poly(acrylamide)-co-poly(vinylimidazole)@MWCNTs composite for use as an electrochemical material.

Ultrason Sonochem 2018 May 21;43:73-79. Epub 2017 Nov 21.

Department of Chemistry, College of Natural Science, Dankook University, Anseo-Dong, Cheonan, Chungnam 31116, Republic of Korea. Electronic address:

Applying a nanocomposite to increase the conductivity of an electrode can facilitate electrochemical analysis. In this regard, multi-walled carbon nanotubes (MWCNTs) evenly dispersed in hydrophilic solution can play an important role in electrochemical bio-sensing due to their unique properties, such as their high electrical conductivity and ability to conjugate with hydrophilic enzymes. Herein, we report the simple ultrasonic synthesis of a highly dispersible, enzyme-binding nanocomposite, poly(acrylamide)-co-poly(vinyl imidazole) (7:1 mol ratio)-MWCNTs ([email protected]). This material, having a zeta potential of 36.6 ± 0.53 mV, was applied as a film to an electrode surface and stably bound with glucose oxidase to transfer an electron between the enzyme and electrode in the presence of glucose. The [email protected] composite, which was readily dispersed in deionized water, can be used as a biocompatible material for applications such as bio-sensing, point-of-care testing (POCT), and other health care functions.
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http://dx.doi.org/10.1016/j.ultsonch.2017.11.024DOI Listing
May 2018

Human Herpesvirus 8 Interferon Regulatory Factors 1 and 3 Mediate Replication and Latency Activities via Interactions with USP7 Deubiquitinase.

J Virol 2018 04 14;92(7). Epub 2018 Mar 14.

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Human herpesvirus 8 (HHV-8) encodes four viral interferon regulatory factors (vIRF-1 to -4) that likely function to suppress innate immune and cellular stress responses through inhibitory interactions with various cellular proteins involved in these activities. It is notable that vIRF-1 and -4 have been reported to interact with the deubiquitinase ubiquitin-specific protease 7 (USP7), substrates of which include p53 and the p53-targeting and -destabilizing ubiquitin E3 ligase MDM2. Structural studies of vIRF-1 and vIRF-4 USP7 binding sequences in association with USP7 have been reported; both involve interactions with N-terminal-domain residues of USP7 via EGPS and ASTS motifs in vIRF-1 and vIRF-4, respectively, but vIRF-4 residues also contact the catalytic site. However, the biological activities of vIRF-1 and vIRF-4 via USP7 interactions are unknown. Here, we report that vIRF-3, which is latently, as well as lytically, expressed in HHV-8-infected primary effusion lymphoma (PEL) cells, also interacts with USP7-via duplicated EGPS motifs-and that this interaction is important for PEL cell growth and viability. The interaction also contributes to suppression of productive virus replication by vIRF-3, which we identify here. We further show that vIRF-1, which is expressed at low levels in PEL latency, promotes latent PEL cell viability and that this activity and vIRF-1-promoted productive replication (reported previously) involve EGPS motif-mediated USP7 targeting by vIRF-1. This study is the first to identify latent and lytic functions of vIRF-1 and vIRF-3, respectively, and to address the biological activities of these vIRFs through their interactions with USP7. HHV-8 is associated with Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease; both latent and lytic viral functions are believed to contribute. Viral interferon regulatory factors specified by HHV-8 are thought to be critically important for successful productive replication through suppression of innate immune and stress responses triggered by the lytic cycle. Latently expressed vIRF-3 contributes significantly to PEL cell survival. Here, we identify ubiquitin-specific protease 7 (USP7) deubiquitinase targeting by vIRF-3 (in addition to previously reported USP7 binding by vIRF-1 and vIRF-4); the importance of vIRF-1 and vIRF-3 interactions with USP7 for latent PEL cell growth and viability; and the positive and negative contributions, respectively, of USP7 targeting by vIRF-1 and vIRF-3 to HHV-8 productive replication. This is the first report of the biological importance of vIRF-1 in PEL cell latency, the modulation of productive replication by vIRF-3, and the contributions of vIRF-USP7 interactions to HHV-8 biology.
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http://dx.doi.org/10.1128/JVI.02003-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972880PMC
April 2018

A Simple Interfacial Platform for Homogeneous Electrochemical Immunoassays Using a Poly(Vinylimidazole)-Modified Electrode.

Sensors (Basel) 2016 Dec 29;17(1). Epub 2016 Dec 29.

Department of Chemistry, College of Natural Science, Dankook University, Anseo-Dong, Cheonan, Chungnam 330-714, Korea.

In this study, a homogeneous method featuring simple, one-step detection was developed to analyze hippuric acid (HA), a major metabolite of toluene. High sensitivity was achieved with the facile immobilization of poly(vinylimidazole) (PVI) on an indium tin oxide (ITO) electrode. Using a previously developed approach, pentacyanoferrate was coordinated with pyridyl- ligands, and the redox-active Fe(II/III) centers were bound to Ni(II) ions on the electrode via electrostatic cyanide bridges. The detection was accomplished by the competitive binding of free HA and pentacyanoferrate-(4-aminomethylpyridine-hippuric acid) (Fe-HA, the electron transfer mediator) to the HA antibody on the Ni(II) ions-modified PVI-ITO (Ni-PVI-ITO) electrode. The electrical and physicochemical characterization of the electrode was carried out by cyclic voltammetry, differential pulse voltammetry, field emission scanning electron microscopy, and X-ray photoelectron spectroscopy. At low mediator concentrations, the electrical signals were proportional to the HA concentration between 0.1 µg/mL and 1.0 mg/mL. The same method may be extended to other small organic molecules.
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http://dx.doi.org/10.3390/s17010054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5298627PMC
December 2016

The Itch ubiquitin ligase is required for KSHV RTA induced vFLIP degradation.

Virology 2017 01 30;501:119-126. Epub 2016 Nov 30.

Department of Biological Sciences, Towson University, 8000 York Rd, Towson, MD 21252, USA. Electronic address:

Expression of Kaposi's sarcoma herpesvirus vFLIP, a potent activator of NFkB signaling, promotes latency. Inhibition of NFkB signaling promotes lytic reactivation. We previously reported that lytic inducer, RTA, inhibits vFLIP induced NFkB signaling by inducing the degradation of vFLIP via the proteasome. Here we report that the cellular ubiquitin ligase, Itch, is required for RTA induced degradation of vFLIP. Expression of either Itch targeting shRNA or a dominant negative mutant of the ubiquitin ligase both increased the stability of vFLIP in the presence of RTA. Itch potently ubiquitinated vFLIP in vivo and in vitro. We provide evidence for interaction between RTA, vFLIP and Itch and we identified an RTA resistant mutant of vFLIP that is unable to interact with Itch. These observations contribute to our understanding of how RTA counteracts the activities of vFLIP.
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http://dx.doi.org/10.1016/j.virol.2016.11.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5271570PMC
January 2017

TAX1BP1 Restrains Virus-Induced Apoptosis by Facilitating Itch-Mediated Degradation of the Mitochondrial Adaptor MAVS.

Mol Cell Biol 2017 01 19;37(1). Epub 2016 Dec 19.

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA

The host response to RNA virus infection consists of an intrinsic innate immune response and the induction of apoptosis as mechanisms to restrict viral replication. The mitochondrial adaptor molecule MAVS plays critical roles in coordinating both virus-induced type I interferon production and apoptosis; however, the regulation of MAVS-mediated apoptosis is poorly understood. Here, we show that the adaptor protein TAX1BP1 functions as a negative regulator of virus-induced apoptosis. TAX1BP1-deficient cells are highly sensitive to apoptosis in response to infection with the RNA viruses vesicular stomatitis virus and Sendai virus and to transfection with poly(I·C). TAX1BP1 undergoes degradation during RNA virus infection, and loss of TAX1BP1 is associated with apoptotic cell death. TAX1BP1 deficiency augments virus-induced activation of proapoptotic c-Jun N-terminal kinase (JNK) signaling. Virus infection promotes the mitochondrial localization of TAX1BP1 and concomitant interaction with the mitochondrial adaptor MAVS. TAX1BP1 recruits the E3 ligase Itch to MAVS to trigger its ubiquitination and degradation, and loss of TAX1BP1 or Itch results in increased MAVS protein expression. Together, these results indicate that TAX1BP1 functions as an adaptor molecule for Itch to target MAVS during RNA virus infection and thus restrict virus-induced apoptosis.
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http://dx.doi.org/10.1128/MCB.00422-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192085PMC
January 2017

Disposable Non-Enzymatic Glucose Sensors Using Screen-Printed Nickel/Carbon Composites on Indium Tin Oxide Electrodes.

Sensors (Basel) 2015 Dec 10;15(12):31083-91. Epub 2015 Dec 10.

Department of Nanobiomedical Sciences and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Anseo-Dong, Cheonan, Chungnam 330-714, Korea.

Disposable screen-printed nickel/carbon composites on indium tin oxide (ITO) electrodes (DSPNCE) were developed for the detection of glucose without enzymes. The DSPNCE were prepared by screen-printing the ITO substrate with a 50 wt% nickel/carbon composite, followed by curing at 400 °C for 30 min. The redox couple of Ni(OH)₂/NiOOH was deposited on the surface of the electrodes via cyclic voltammetry (CV), scanning from 0-1.5 V for 30 cycles in 0.1 M NaOH solution. The DSPNCE were characterized by field-emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), and electrochemical methods. The resulting electrical currents, measured by CV and chronoamperometry at 0.65 V vs. Ag/AgCl, showed a good linear response with glucose concentrations from 1.0-10 mM. Also, the prepared electrodes showed no interference from common physiologic interferents such as uric acid (UA) or ascorbic acid (AA). Therefore, this approach allowed the development of a simple, disposable glucose biosensor.
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http://dx.doi.org/10.3390/s151229846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721766PMC
December 2015

Modulation of Mitochondrial Antiviral Signaling by Human Herpesvirus 8 Interferon Regulatory Factor 1.

J Virol 2016 01 28;90(1):506-20. Epub 2015 Oct 28.

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Unlabelled: Mitochondrial lipid raft-like microdomains, experimentally also termed mitochondrial detergent-resistant membrane fractions (mDRM), play a role as platforms for recruiting signaling molecules involved in antiviral responses such as apoptosis and innate immunity. Viruses can modulate mitochondrial functions for their own survival and replication. However, viral regulation of the antiviral responses via mDRM remains incompletely understood. Here, we report that human herpesvirus 8 (HHV-8) gene product viral interferon regulatory factor 1 (vIRF-1) is targeted to mDRM during virus replication and negatively regulates the mitochondrial antiviral signaling protein (MAVS)-mediated antiviral responses. The N-terminal region of vIRF-1 interacts directly with membrane lipids, including cardiolipin. In addition, a GxRP motif within the N terminus of vIRF-1, conserved in the mDRM-targeting region of mitochondrial proteins, including PTEN-induced putative kinase 1 (PINK1) and MAVS, was found to be important for vIRF-1 association with mitochondria. Furthermore, MAVS, which has the potential to promote vIRF-1 targeting to mDRM possibly by inducing cardiolipin exposure on the outer membrane of mitochondria, interacts with vIRF-1, which, in turn, inhibits MAVS-mediated antiviral signaling. Consistent with these results, vIRF-1 targeting to mDRM contributes to promotion of HHV-8 productive replication and inhibition of associated apoptosis. Combined, our results suggest novel molecular mechanisms for negative-feedback regulation of MAVS by vIRF-1 during virus replication.

Importance: Successful virus replication is in large part achieved by the ability of viruses to counteract apoptosis and innate immune responses elicited by infection of host cells. Recently, mitochondria have emerged to play a central role in antiviral signaling. In particular, mitochondrial lipid raft-like microdomains appear to function as platforms in cell apoptosis signaling. However, viral regulation of antiviral signaling through the mitochondrial microdomains remains incompletely understood. The present study demonstrates that HHV-8-encoded vIRF-1 targets to the mitochondrial detergent-resistant microdomains via direct interaction with cardiolipin and inhibits MAVS protein-mediated apoptosis and type I interferon gene expression in a negative-feedback manner, thus promoting HHV-8 productive replication. These results suggest that vIRF-1 is the first example of a viral protein to inhibit mitochondrial antiviral signaling through lipid raft-like microdomains.
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http://dx.doi.org/10.1128/JVI.01903-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702585PMC
January 2016

Functional implications of mitochondrial reactive oxygen species generated by oncogenic viruses.

Front Biol (Beijing) 2014 Dec;9(6):423-436

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns HopkinsSchool of Medicine, Baltimore, MD 21287, USA.

Between 15-20% of human cancers are associated with infection by oncogenic viruses. Oncogenic viruses, including HPV, HBV, HCV and HTLV-1, target mitochondria to influence cell proliferation and survival. Oncogenic viral gene products also trigger the production of reactive oxygen species which can elicit oxidative DNA damage and potentiate oncogenic host signaling pathways. Viral oncogenes may also subvert mitochondria quality control mechanisms such as mitophagy and metabolic adaptation pathways to promote virus replication. Here, we will review recent progress on viral regulation of mitophagy and metabolic adaptation and their roles in viral oncogenesis.
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http://dx.doi.org/10.1007/s11515-014-1332-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286258PMC
December 2014

HTLV-1 tax stabilizes MCL-1 via TRAF6-dependent K63-linked polyubiquitination to promote cell survival and transformation.

PLoS Pathog 2014 Oct 23;10(10):e1004458. Epub 2014 Oct 23.

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.

The human T-cell leukemia virus type 1 (HTLV-1) Tax protein hijacks the host ubiquitin machinery to activate IκB kinases (IKKs) and NF-κB and promote cell survival; however, the key ubiquitinated factors downstream of Tax involved in cell transformation are unknown. Using mass spectrometry, we undertook an unbiased proteome-wide quantitative survey of cellular proteins modified by ubiquitin in the presence of Tax or a Tax mutant impaired in IKK activation. Tax induced the ubiquitination of 22 cellular proteins, including the anti-apoptotic BCL-2 family member MCL-1, in an IKK-dependent manner. Tax was found to promote the nondegradative lysine 63 (K63)-linked polyubiquitination of MCL-1 that was dependent on the E3 ubiquitin ligase TRAF6 and the IKK complex. Tax interacted with and activated TRAF6, and triggered its mitochondrial localization, where it conjugated four carboxyl-terminal lysine residues of MCL-1 with K63-linked polyubiquitin chains, which stabilized and protected MCL-1 from genotoxic stress-induced degradation. TRAF6 and MCL-1 played essential roles in the survival of HTLV-1 transformed cells and the immortalization of primary T cells by HTLV-1. Therefore, K63-linked polyubiquitination represents a novel regulatory mechanism controlling MCL-1 stability that has been usurped by a viral oncogene to precipitate cell survival and transformation.
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http://dx.doi.org/10.1371/journal.ppat.1004458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207805PMC
October 2014

Heterogeneous electrochemical immunoassay of hippuric acid on the electrodeposited organic films.

Sensors (Basel) 2014 Oct 13;14(10):18886-97. Epub 2014 Oct 13.

Department of chemistry, College of Natural Science, Dankook University, Anseo-Dong, Cheonan 330-714, Korea.

By directly coordinating hippuric acid (HA) to the ferrate (Fe) as an electron transfer mediator, we synthesized a Fe-HA complex, which shows a good electrochemical signal and thus enables the electrochemical immunoanalysis for HA. We electrodeposited organic films containing imidazole groups on the electrode surface and then bonded Ni ion (positive charge) to induce immobilization of Fe-HA (negative charge) through the electrostatic interaction. The heterogeneous competitive immunoassay system relies on the interaction between immobilized Fe-HA antigen conjugate and free HA antigen to its antibody (anti-HA). The electric signal becomes weaker due to the hindered electron transfer reaction when a large-sized HA antibody is bound onto the Fe-HA. However, in the presence of HA, the electric signal increases because free HA competitively reacts with the HA antibody prior to actual reaction and thus prevents the HA antibody from interacting with Fe-HA at the electrode surface. This competition reaction enabled an electrochemical quantitative analysis of HA concentration with a detection limit of 0.5 μg mL(-1), and thus allowed us to develop a simple and rapid electrochemical immunosensor.
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http://dx.doi.org/10.3390/s141018886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239960PMC
October 2014

High-power biofuel cell textiles from woven biscrolled carbon nanotube yarns.

Nat Commun 2014 Jun 2;5:3928. Epub 2014 Jun 2.

Center for Bio-Artificial Muscle and Department of Biomedical Engineering, Hanyang University, Seoul 133-791, Korea.

Biofuel cells that generate electricity from glucose in blood are promising for powering implantable biomedical devices. Immobilizing interconnected enzyme and redox mediator in a highly conducting, porous electrode maximizes their interaction with the electrolyte and minimizes diffusion distances for fuel and oxidant, thereby enhancing power density. Here we report that our separator-free carbon nanotube yarn biofuel cells provide an open-circuit voltage of 0.70 V, and a maximum areal power density of 2.18 mW cm(-2) that is three times higher than for previous carbon nanotube yarn biofuel cells. Biofuel cell operation in human serum provides high areal power output, as well as markedly increased lifetime (83% remained after 24 h), compared with previous unprotected biofuel cells. Our biscrolled yarn biofuel cells are woven into textiles having the mechanical robustness needed for implantation for glucose energy harvesting.
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http://dx.doi.org/10.1038/ncomms4928DOI Listing
June 2014

Homogeneous electrochemical detection of hippuric acid in urine based on the osmium-antigen conjugate.

Chemphyschem 2013 Jul 15;14(10):2331-7. Epub 2013 Apr 15.

Department of Nanobiomedical Science & WCU Research Center, Dankook University, Cheonan 330-714, Republic of Korea.

A homogeneous electrochemical immunoassay is based on the interaction of osmium-antigen conjugate with its antibody. The novelty presented herein is the direct conjugation of the osmium complex to a small antigen and the application of the quantitative analysis of the antigen and its antibody as the electrical signal for homogeneous immunoassay. The small antigen chosen is hippuric acid (HA), a major urinary metabolite in toluene-exposed humans. As a redox mediator, [Os(4,4'-dimethoxy-2,2'-bipyridine)2(4-aminomethylpyridine-HA)Cl](+/2+) (Os-HA antigen) has been synthesized and characterized on screen-printed carbon electrodes. The synthesized Os-HA antigen shows reversible redox peaks at E(½)=0.056 V versus Ag/AgCl. The homogeneous competitive immunoassay relies on the interaction between Os-HA antigen conjugate and free antigen to its antibody, which can generate electrical signals linearly proportional to the free antigen monitored by cyclic voltammetry and differential pulse voltammetry in the range of 10 μg mL(-1) to 5.12 mg mL(-1). The cutoff concentration of HA in urine samples is 2.0 mg mL(-1), so the method can be used to develop a HA immunosensor. Moreover, the proposed homogeneous electrochemical immunoassay method can be applied to detect low concentrations of small antigens found in the healthcare area.
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http://dx.doi.org/10.1002/cphc.201300039DOI Listing
July 2013

Human herpesvirus 8 interferon regulatory factor-mediated BH3-only protein inhibition via Bid BH3-B mimicry.

PLoS Pathog 2012 7;8(6):e1002748. Epub 2012 Jun 7.

Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.

Viral replication efficiency is in large part governed by the ability of viruses to counteract pro-apoptotic signals induced by infection of host cells. For HHV-8, viral interferon regulatory factor-1 (vIRF-1) contributes to this process in part via inhibitory interactions with BH3-only protein (BOP) Bim, recently identified as an interaction partner of vIRF-1. Here we recognize that the Bim-binding domain (BBD) of vIRF-1 resembles a region (BH3-B) of Bid, another BOP, which interacts intramolecularly with the functional BH3 domain of Bid to inhibit it pro-apoptotic activity. Indeed, vIRF-1 was found to target Bid in addition to Bim and to interact, via its BBD region, with the BH3 domain of each. In functional assays, BBD could substitute for BH3-B in the context of Bid, to suppress Bid-induced apoptosis in a BH3-binding-dependent manner, and vIRF-1 was able to protect transfected cells from apoptosis induced by Bid. While vIRF-1 can mediate nuclear sequestration of Bim, this was not the case for Bid, and inhibition of Bid and Bim by vIRF-1 could occur independently of nuclear localization of the viral protein. Consistent with this finding, direct BBD-dependent inactivation by vIRF-1 of Bid-induced mitochondrial permeabilization was demonstrable in vitro and isolated BBD sequences were also active in this assay. In addition to Bim and Bid BH3 domains, BH3s of BOPs Bik, Bmf, Hrk, and Noxa also were found to bind BBD, while those of both pro- and anti-apoptotic multi-BH domain Bcl-2 proteins were not. Finally, the significance of Bid to virus replication was demonstrated via Bid-depletion in HHV-8 infected cells, which enhanced virus production. Together, our data demonstrate and characterize BH3 targeting and associated inhibition of BOP pro-apoptotic activity by vIRF-1 via Bid BH3-B mimicry, identifying a novel mechanism of viral evasion from host cell defenses.
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http://dx.doi.org/10.1371/journal.ppat.1002748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3369933PMC
November 2012

Assurance of mitochondrial integrity and mammalian longevity by the p62-Keap1-Nrf2-Nqo1 cascade.

EMBO Rep 2012 Feb 1;13(2):150-6. Epub 2012 Feb 1.

Sungkyunkwan University School of Medicine and Samsung Biomedical Research Institute, Suwon-Si, Kyonggi-Do 440-746, Korea.

Sqstm1/p62 functions in the non-canonical activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). However, its physiological relevance is not certain. Here, we show that p62(-/-) mice exhibited an accelerated presentation of ageing phenotypes, and tissues from these mice created a pro-oxidative environment owing to compromised mitochondrial electron transport. Accordingly, mitochondrial function rapidly declined with age in p62(-/-) mice. In addition, p62 enhanced basal Nrf2 activity, conferring a higher steady-state expression of NAD(P)H dehydrogenase, quinone 1 (Nqo1) to maintain mitochondrial membrane potential and, thereby, restrict excess oxidant generation. Together, the p62-Nrf2-Nqo1 cascade functions to assure mammalian longevity by stabilizing mitochondrial integrity.
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http://dx.doi.org/10.1038/embor.2011.246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3271336PMC
February 2012

Bim nuclear translocation and inactivation by viral interferon regulatory factor.

PLoS Pathog 2010 Aug 5;6(8):e1001031. Epub 2010 Aug 5.

Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.

Viral replication efficiency is in large part governed by the ability of viruses to counteract pro-apoptotic signals induced by infection of the host cell. Human herpesvirus 8 (HHV-8) uses several strategies to block the host's innate antiviral defenses via interference with interferon and apoptotic signaling. Contributors include the four viral interferon regulatory factors (vIRFs 1-4), which function in dominant negative fashion to block cellular IRF activities in addition to targeting IRF signaling-induced proteins such as p53 and inhibiting other inducers of apoptosis such as TGFbeta receptor-activated Smad transcription factors. Here we identify direct targeting by vIRF-1 of BH3-only pro-apoptotic Bcl-2 family member Bim, a key negative regulator of HHV-8 replication, to effect its inactivation via nuclear translocation. vIRF-1-mediated relocalization of Bim was identified in transfected cells, by both immunofluorescence assay and western analysis of fractionated cell extracts. Also, co-localization of vIRF-1 and Bim was detected in nuclei of lytically infected endothelial cells. In vitro co-precipitation assays using purified vIRF-1 and Bim revealed direct interaction between the proteins, and Bim-binding residues of vIRF-1 were mapped by deletion and point mutagenesis. Generation and experimental utilization of Bim-refractory vIRF-1 variants revealed the importance of vIRF-1:Bim interaction, specifically, in pro-replication and anti-apoptotic activity of vIRF-1. Furthermore, blocking of the interaction with cell-permeable peptide corresponding to the Bim-binding region of vIRF-1 confirmed the relevance of vIRF-1:Bim association to vIRF-1 pro-replication activity. To our knowledge, this is the first report of an IRF protein that interacts with a Bcl-2 family member and of nuclear sequestration of Bim or any other member of the family as a means of inactivation. The data presented reveal a novel mechanism utilized by a virus to control replication-induced apoptosis and suggest that inhibitory targeting of vIRF-1:Bim interaction may provide an effective antiviral strategy.
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http://dx.doi.org/10.1371/journal.ppat.1001031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916877PMC
August 2010

SOCS-6 negatively regulates T cell activation through targeting p56lck to proteasomal degradation.

J Biol Chem 2010 Mar 10;285(10):7271-80. Epub 2009 Dec 10.

Department of Life Science, Ewha Woman's University, 120-750 Seoul, Korea.

The T cell-specific tyrosine kinase, p56(lck), plays crucial roles in T cell receptor (TCR)-mediated T cell activation. Here, we report that SOCS-6 (suppressor of cytokine signaling-6) is a negative regulator of p56(lck). SOCS-6 was identified as a protein binding to the kinase domain of p56(lck) through yeast two-hybrid screening. SOCS-6 bound specifically to p56(lck) (F505), which mimics the active form of p56(lck), but not to wild type p56(lck). In Jurkat T cells, SOCS-6 binding to p56(lck) was detected 1-2 h after TCR stimulation. Confocal microscopy showed that upon APC-T cell conjugation, SOCS-6 was recruited to the immunological synapse and colocalized with the active form of p56(lck). SOCS-6 promoted p56(lck) ubiquitination and its subsequent targeting to the proteasome. Moreover, SOCS-6 overexpression led to repression of TCR-dependent interleukin-2 promoter activity. These results establish that SOCS-6 acts as a negative regulator of T cell activation by promoting ubiquitin-dependent proteolysis.
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http://dx.doi.org/10.1074/jbc.M109.073726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844175PMC
March 2010

Induction of angiogenic chemokine CCL2 by human herpesvirus 8 chemokine receptor.

Virology 2010 Feb 9;397(2):369-78. Epub 2009 Dec 9.

Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

Human herpesvirus 8 (HHV-8) is associated with Kaposi's sarcoma (KS), an endothelial cell lesion believed to be initiated and driven primarily by cytokine dysregulation. Among the viral proteins suspected as contributing to viral pathogenesis is the lytically expressed viral G protein-coupled receptor (vGPCR), which can induce various cellular cytokines. CC ligand-2 (CCL2/MCP-1) is a vGPCR-regulated angiogenic chemokine found at elevated levels in KS lesions and induced by HHV-8 infection of endothelial cells. Here we show that vGPCR induces CCL2 in endothelial cells via activation of C/EBPbeta and that vGPCR and C/EBPbeta are critical components of CCL2 induction by HHV-8 infection of endothelial cultures. To our knowledge, this is the first report of vGPCR-mediated cytokine induction, and its characterization, in the context of virus infection. Our results identify a mechanism by which vGPCR can contribute, in a host cell shutoff-independent manner, to viral pathogenesis.
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http://dx.doi.org/10.1016/j.virol.2009.11.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024549PMC
February 2010
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