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Viruses, Vol. 14, Pages 2004: Human Cytomegalovirus Induces Vitamin-D Resistance In Vitro by Dysregulating the Transcriptional Repressor Snail
In this study, we aimed to elucidate the mechanism and possible biological consequences of vitamin-D resistance during HCMV infection. Mechanistically, HCMV induced vitamin-D resistance by downregulating the vitamin-D receptor (VDR) within hours of lytic infection. We found that the VDR was inhibited at the promoter level, and treatment with histone deacetylase inhibitors could restore VDR expression. VDR downregulation highly correlated with the upregulation of the transcriptional repressor Snail1, a mechanism likely contributing to the epigenetic inactivation of the VDR promoter, since siRNA-mediated knockdown of Snail p...
Source: Viruses - September 10, 2022 Category: Virology Authors: Carmen Stecher Katharina Philomena Maurer Marie-Theres Kastner Christoph Steininger Tags: Article Source Type: research

Immediately early 2 (IE-2) and DNA polymerase SiRNA as virus-specific antiviral against novel transplacental cytomegalovirus strain ALL-03 in vitro
CONCLUSION: In conclusion, this study clearly highlighted the feasibility of RNAi as an alternative antiviral therapy that could lead to controlling the CMV infection.PMID:33640483 | DOI:10.1016/j.meegid.2021.104783
Source: Infection, Genetics and Evolution - February 28, 2021 Category: Genetics & Stem Cells Authors: Krishnan Nair Balakrishnan Ashwaq Ahmed Abdullah Jamilu Abubakar Bala Faez Firdaus Abdullah Jesse Che Azurahanim Che Abdullah Mustapha Mohamed Noordin Mohd Lila Mohd-Azmi Source Type: research

Vector derived artificial miRNA mediated inhibition of West Nile virus replication and protein expression.
Abstract West Nile virus (WNV) has been found to be a common cause of neuroinvasive arboviral disease worldwide in human and horses. The process of RNA interference induced by small RNA molecules, like small interfering RNA (siRNA) and microRNA (miRNA), proved to be a novel approach for preventing viral infections. So far there is no published data for inhibition of West Nile virus by vector delivered artificial miRNA which believed to have more inhibitory potential than small interfering (siRNA). In the present study, we designed two artificial miRNA (amiRNAs) targeting the conserved NS5 and NS2A genomic regions ...
Source: Gene - December 25, 2019 Category: Genetics & Stem Cells Authors: Karothia D, Kumar Dash P, Parida M, Bhagyawant SS, S Kumar J Tags: Gene Source Type: research

Gene Therapy Leaves a Vicious Cycle
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - April 23, 2019 Category: Cancer & Oncology Source Type: research

Oligonucleotides —A Novel Promising Therapeutic Option for IBD
Conclusions In this review, we focused on recent and past approaches to test the therapeutic efficacy of oligonucleotide based therapies in IBD. The combining mechanistic mode of oligonucleotide based therapeutics is a targeted action on specific pro-inflammatory molecules, which are over activated in IBD patients and contribute significantly to disease pathogenesis. The proposed high selectivity of the agents is derived from its mode of action, that aims to specifically block certain inflammatory molecular patterns, without a general systemic effect on other molecular targets. It would be important for each oligonucleot...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Modeling Modulation of the Tick Regulome in Response to Anaplasma phagocytophilum for the Identification of New Control Targets
Conclusion Our modeling of the modulation of the tick regulome in response to A. phagocytophilum infection provided new insights into the mechanisms that target specific functions in different tick tissues. These results supported the use of network analysis for the study of regulome response to infection. Although general mechanisms affected by A. phagocytophilum infection may be conserved even between tick and human cells (de la Fuente et al., 2016b), the effect of vector-pathogen co-evolution on pathogen isolates adaptation to grow in tick cells (Alberdi et al., 2015) may result in differences between isolates in the m...
Source: Frontiers in Physiology - April 17, 2019 Category: Physiology Source Type: research

SOCS and Herpesviruses, With Emphasis on Cytomegalovirus Retinitis
Christine I. Alston1,2 and Richard D. Dix1,2* 1Department of Biology, Viral Immunology Center, Georgia State University, Atlanta, GA, United States 2Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, United States Suppressor of cytokine signaling (SOCS) proteins provide selective negative feedback to prevent pathogeneses caused by overstimulation of the immune system. Of the eight known SOCS proteins, SOCS1 and SOCS3 are the best studied, and systemic deletion of either gene causes early lethality in mice. Many viruses, including herpesviruses such as herpes simplex virus and cytomega...
Source: Frontiers in Immunology - April 10, 2019 Category: Allergy & Immunology Source Type: research

Mitochondrial respiratory chain deficiency inhibits lysosomal hydrolysis.
Abstract Mitochondria are key organelles for cellular metabolism, and regulate several processes including cell death and macroautophagy/autophagy. Here, we show that mitochondrial respiratory chain (RC) deficiency deactivates AMP-activated protein kinase (AMPK, a key regulator of energy homeostasis) signaling in tissue and in cultured cells. The deactivation of AMPK in RC-deficiency is due to increased expression of the AMPK-inhibiting protein FLCN (folliculin). AMPK is found to be necessary for basal lysosomal function, and AMPK deactivation in RC-deficiency inhibits lysosomal function by decreasing the activity...
Source: Autophagy - March 26, 2019 Category: Cytology Authors: Fernandez-Mosquera L, Yambire KF, Couto R, Pereyra L, Pabis K, Ponsford AH, Diogo CV, Stagi M, Milosevic I, Raimundo N Tags: Autophagy Source Type: research

Role of vasodilator-stimulated phosphoprotein in human cytomegalovirus-induced hyperpermeability of human endothelial cells.
Authors: Tian Y, He Y, Zhang L, Zhang J, Xu L, Ma Y, Xu X, Wei L Abstract Atherosclerosis (AS) is a common chronic vascular disease and epidemiological evidence demonstrates that infection is closely associated with the occurrence of AS, including infection by human cytomegalovirus (HCMV) and Chlamydophila pneumoniae. The aim of the present study was to investigate the effect of HCMV AD169 infection on the barrier function of human umbilical vein endothelial cells (HUVECs) and to understand the role of vasodilator-stimulated phosphoprotein (VASP) during this process. In cultured HUVEC-CRL-1730 cells, knockdown of V...
Source: Experimental and Therapeutic Medicine - August 18, 2018 Category: General Medicine Tags: Exp Ther Med Source Type: research

Identification of KX2-391 as an inhibitor of HBV transcription by a recombinant HBV-based screening assay
This study used recombinant HBV encoding NanoLuc to screen anti-HBV compounds from 1827 US Food and Drug Administration approved compounds and identified several compounds that suppressed HBV infection. Among them, KX2-391, a non-ATP-competitive inhibitor of SRC kinase and tubulin polymerization, was identified as a lead candidate for an anti-HBV drug. Treatment of sodium taurocholate cotransporting polypeptide (NTCP) transduced-HepG2 (HepG2-NTCP) or primary human hepatocytes with KX2-391 suppressed HBV replication in a dose-dependent manner. The anti-HBV activity of KX2-391 appeared not to depend on SRC kinase activity be...
Source: Antiviral Therapy - June 16, 2017 Category: Virology Source Type: research

Identification of KX2-391 as an inhibitor of HBV transcription by a recombinant HBV-based screening assay.
This study used recombinant HBV encoding NanoLuc to screen anti-HBV compounds from 1827 US Food and Drug Administration approved compounds and identified several compounds that suppressed HBV infection. Among them, KX2-391, a non-ATP-competitive inhibitor of SRC kinase and tubulin polymerization, was identified as a lead candidate for an anti-HBV drug. Treatment of sodium taurocholate cotransporting polypeptide (NTCP) transduced-HepG2 (HepG2-NTCP) or primary human hepatocytes with KX2-391 suppressed HBV replication in a dose-dependent manner. The anti-HBV activity of KX2-391 appeared not to depend on SRC kinase activity be...
Source: Antiviral Research - June 14, 2017 Category: Virology Authors: Harada K, Nishitsuji H, Ujino S, Shimotohno K Tags: Antiviral Res Source Type: research

The viral G protein-coupled receptor ORF74 unmasks phospholipase C signaling of the receptor tyrosine kinase IGF-1R.
In this study we examined the effect of the constitutively active viral ORF74 on human IGF-1R signaling. Constitutive and CXCL1-induced ORF74 signaling did not transactivate IGF-1R. In contrast, IGF-1 stimulated phospholipase C (PLC) activation in an ORF74-dependent manner without affecting chemokine binding to ORF74. Inhibition of constitutive ORF74 activity by mutagenesis or the inverse agonist CXCL10, or neutralizing IGF-1R with an antibody or silencing IGF-1R expression using siRNA inhibited PLC activation by IGF-1. Transactivation of ORF74 in response to IGF-1 occurred independently of Src, PI3K, and secreted ORF74 li...
Source: Cellular Signalling - February 27, 2016 Category: Cytology Authors: de Munnik SM, van der Lee R, Velders DM, van Offenbeek J, Smits-de Vries L, Leurs R, Smit MJ, Vischer HF Tags: Cell Signal Source Type: research

Abstract 2958: Discovering therapeutic epigenetic targets using whole genome siRNA screening
Conclusions: A whole genome siRNA screen in combination with the DNMT inhibitor decitabine identified many new target genes that might be epigenetic regulators and potential targets for drug development.Citation Format: Yasuyuki Okamoto, Woonbok Chung, Judith Garriga, Jaroslav Jelinek, Jean-Pierre J. Issa. Discovering therapeutic epigenetic targets using whole genome siRNA screening. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2958. doi:10.1158/1538-7445.AM2015-2958
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Okamoto, Y., Chung, W., Garriga, J., Jelinek, J., Issa, J.-P. J. Tags: Molecular and Cellular Biology Source Type: research

Human cytomegalovirus miR-UL36-5p inhibits apoptosis via downregulation of adenine nucleotide translocator 3 in cultured cells
In this study, ANT3 was further demonstrated to be a direct target of hcmv-miR-UL36-5p by luciferase reporter assays. The expression level of ANT3 protein was confirmed, by western blotting, to be directly downregulated by overexpression of hcmv-miR-UL36-5p in HEK293 cells, U373 cells and HELF cells. Moreover, HCMV-infected cells showed a decrease in the ANT3 protein level. Using ANT3-specific small interfering RNA (siRNA) and an inhibitor for hcmv-miR-UL36-5p, it was shown that inhibition of apoptosis by hcmv-miR-UL36-5p in these cells specifically occurred via inhibition of ANT3 expression. These results imply that hcmv-...
Source: Archives of Virology - July 28, 2015 Category: Virology Source Type: research

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