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Infectious Disease: Cytomegalovirus

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Total 27 results found since Jan 2013.

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

Epstein-Barr virus glycoprotein gM can interact with the cellular protein p32 and knockdown of p32 impairs virus.
We report here that the long predicted cytoplasmic tail of gM is not required for complex formation and that it interacts with the cellular protein p32, which has been reported to be involved in nuclear egress of human cytomegalovirus and herpes simplex virus. Although redistribution of p32 and colocalization with gM was not observed in virus infected cells, knockdown of p32 expression by siRNA or lentivirus-delivered shRNA recapitulated the phenotype of a virus lacking expression of gNgM. A proportion of virus released from cells sedimented with characteristics of virus lacking an intact envelope and there was an increase...
Source: Virology - January 13, 2016 Category: Virology Authors: Changotra H, Turk SM, Artigues A, Thakur N, Gore M, Muggeridge MI, Hutt-Fletcher LM Tags: Virology 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

Human cytomegalovirus triggers the assembly of AIM2 inflammasome in THP ‐1‐derived macrophages
In conclusion, HCMV infection induces an AIM2 inflammasome response, which negatively influences viral life cycle. This article is protected by copyright. All rights reserved
Source: Journal of Medical Virology - May 8, 2017 Category: Virology Authors: Yuan Huang, Lingling Liu, Di Ma, Yi Liao, Yuanyuan Lu, Heyu Huang, Wenqing Qin, Xinglou Liu, Feng Fang Tags: Research Article 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

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

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

Degradation of SAMHD1 Restriction Factor Through Cullin-Ring E3 Ligase Complexes During Human Cytomegalovirus Infection
Sterile alpha motif (SAM) and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) acts as a restriction factor for several RNA and DNA viruses by limiting the intracellular pool of deoxynucleoside triphosphates. Here, we investigated the regulation of SAMHD1 expression during human cytomegalovirus (HCMV) infection. SAMHD1 knockdown using shRNA increased the activity of the viral UL99 late gene promoter in human fibroblasts by 7- to 9-fold, confirming its anti-HCMV activity. We also found that the level of SAMHD1 was initially increased by HCMV infection but decreased partly at the protein level at late stages of ...
Source: Frontiers in cellular and infection microbiology - July 29, 2020 Category: Microbiology Source Type: research

Rat and human cytomegalovirus ORF116 encodes a virion envelope glycoprotein required for infectivity
Virology. 2021 Feb 9;557:23-33. doi: 10.1016/j.virol.2020.12.014. Online ahead of print.ABSTRACTHerpesviruses encode multiple glycoproteins required for different stages of viral attachment, fusion, and envelopment. The protein encoded by the human cytomegalovirus (HCMV) open reading frame UL116 forms a stable complex with glycoprotein H that is incorporated into virions. However, the function of this complex remains unknown. Herein, we characterize R116, the rat CMV (RCMV) putative homolog of UL116. Two R116 transcripts were identified in fibroblasts with three proteins expressed with molecular weights of 42, 58, and 82 k...
Source: Virology - February 18, 2021 Category: Virology Authors: Philippe Gatault Iris K A Jones Christine Meyer Craig Kreklywich Timothy Alexander Patricia P Smith Michael Denton Josh Powell Susan L Orloff Daniel N Streblow Source Type: research

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