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Chong Huang, Xiao-Hua Yu, Xi-Long Zheng, Xiang Ou, Chao-Ke Tang
Macrophage autophagy contributes to the hydrolysis of cholesteryl ester into free cholesterol mainly for ATP-binding cassette transporter A1 (ABCA1)-dependent efflux. Interferon-stimulated gene 15 (ISG15) has been shown to regulate autophagy in multiple types of cells. The present study aimed to examine the effects of ISG15 on autophagy and cholesterol efflux in THP-1 macrophage-derived foam cells and to explore the underlying molecular mechanisms. Our results showed that overexpression of ISG15 promoted autophagy and cholesterol efflux and inhibited lipid accumulation without impact on ABCA1 expression...
March 5, 2018: European Journal of Pharmacology
Le Guo, Xi-Qiu Xu, Li Zhou, Run-Hong Zhou, Xu Wang, Jie-Liang Li, Jin-Biao Liu, Hang Liu, Biao Zhang, Wen-Zhe Ho
As a rich source of CD4+ T cells and macrophages, the gastrointestinal (GI) tract is a major target site for HIV infection. The interplay between GI-resident macrophages and intestinal epithelial cells (IECs) constitutes an important element of GI innate immunity against pathogens. In this study, we investigated whether human IECs have the ability to produce antiviral factors that can inhibit HIV infection of macrophages. We demonstrated that IECs possess functional toll-like receptor 3 (TLR3), the activation of which resulted in induction of key interferon (IFN) regulatory factors (IRF3 and IRF7), IFN-β, IFN-λ, and CC chemokines (MIP-1α, MIP-1β, RANTES), the ligands of HIV entry co-receptor CCR5...
2018: Frontiers in Immunology
Alexander J Gill, Rolando Garza, Surendra S Ambegaokar, Benjamin B Gelman, Dennis L Kolson
BACKGROUND: Heme oxygenase-1 (HO-1) is a critical cytoprotective enzyme that limits oxidative stress, inflammation, and cellular injury within the central nervous system (CNS) and other tissues. We previously demonstrated that HO-1 protein expression is decreased within the brains of HIV+ subjects and that this HO-1 reduction correlates with CNS immune activation and neurocognitive dysfunction. To define a potential CNS protective role for HO-1 against HIV, we analyzed a well-characterized HIV autopsy cohort for two common HO-1 promoter region polymorphisms that are implicated in regulating HO-1 promoter transcriptional activity, a (GT)n dinucleotide repeat polymorphism and a single nucleotide polymorphism (A(-413)T)...
March 6, 2018: Journal of Neuroinflammation
Rahul Krishnan, Jeena K, Zahoor Mushtaq, K U Shyam, Pani Prasad Kurcheti
The innate immune signaling adapter, Mitochondrial antiviral signaling protein (MAVS) coordinates the signals received from two independent RLRs (RIG-1 and MDA5) to induce IFN & interferon stimulatory genes (ISGs). In the present study, we report identification of an orthologue of MAVS from Lates calcarifer (LcMAVS) and its functional role in piscine RLR signaling. The LcMAVS-cDNA was cloned into pcDNA and transfected into SISS cells. LcMAVS was detected to be a 61KDa protein in western blot. Confocal microscopy demonstrated the mitochondrial localization of LcMAVS...
March 3, 2018: Fish & Shellfish Immunology
Lijie Gao, Yunqi Wang, Yi Li, Ya Dong, Aimin Yang, Jie Zhang, Fengying Li, Rongqiang Zhang
Objectives Comprehensive bioinformatics analyses were performed to explore the key biomarkers in response to HIV infection of CD4+ and CD8+ T cells. Methods The numbers of CD4+ and CD8+ T cells of HIV infected individuals were analyzed and the GEO database (GSE6740) was screened for deferentially expressed genes (DEGs) in HIV infected CD4+ and CD8+ T cells. Gene Ontology enrichment, KEGG pathway analyses and protein-protein interaction (PPI) network were performed to identify the key pathway and core proteins in anti-HIV virus process of CD4+ and CD8+ T cells...
March 6, 2018: Journal of Medical Virology
Moein Farshchian, Maryam M Matin, Olivier Armant, Dirk Geerts, Mahtab Dastpak, Saeideh Nakhaei-Rad, Massoumeh Tajeran, Amir Jebelli, Mina Shahriyari, Monireh Bahrami, Ali Fallah, Vesal Yaghoobi, Mahdi Mirahmadi, Mohammad Reza Abbaszadegan, Ahmad Reza Bahrami
The self-renewal capacity of germline derived stem cells (GSCs) makes them an ideal source for research and use in clinics. Despite the presence of active gene network similarities between embryonic stem cells (ESCs) and GSCs, there are unanswered questions regarding the roles of evolutionary conserved genes in GSCs. To determine the reprogramming potential of germ cell- specific genes, we designed a polycistronic gene cassette expressing Stella, Oct4 and Nanos2 in a lentiviral-based vector. Deep transcriptome analysis showed the activation of a set of pluripotency and germ-cell-specific markers and the downregulation of innate immune system...
March 1, 2018: Cytokine
Prashant Jain, Guney Boso, Simon Langer, Stephen Soonthornvacharin, Paul D De Jesus, Quy Nguyen, Kevin C Olivieri, Alex J Portillo, Sunnie M Yoh, Lars Pache, Sumit K Chanda
Accessory proteins of lentiviruses, such as HIV-1, target cellular restriction factors to enhance viral replication. Systematic analyses of proteins that are targeted for degradation by HIV-1 accessory proteins may provide a better understanding of viral immune evasion strategies. Here, we describe a high-throughput platform developed to study cellular protein stability in a highly parallelized matrix format. We used this approach to identify cellular targets of the HIV-1 accessory protein Vpu through arrayed coexpression with 433 interferon-stimulated genes, followed by differential fluorescent labeling and automated image analysis...
February 27, 2018: Cell Reports
Sajad Ahmad Wani, Amit Ranjan Sahu, Shikha Saxena, Kaushal Kishor Rajak, M Saminathan, Aditya Prasad Sahoo, Sonam Kanchan, Aruna Pandey, Bina Mishra, D Muthuchelvan, Ashok Kumar Tiwari, Bishnu Prasad Mishra, Raj Kumar Singh, Ravi Kumar Gandham
Here, we studied the in vivo expression of Th1 (IL2 and IFN gamma) and Th2 (IL4 and IL10) - cytokines and antiviral molecules - IRF3 and ISG15 in peripheral blood mononuclear cells in relation to antigen and antibody dynamics under Peste des petits ruminants virus (PPRV) vaccination, infection and challenge in both sheep and goats. Vaccinated goats were seropositive by 9 days post vaccination (dpv) while in sheep idiosyncratic response was observed between 9 and 14 dpv for different animals. Expression of PPRV N gene was not detected in PBMCs of vaccinated and vaccinated challenged groups of both species, but was detected in unvaccinated infected PBMCs at 9 and 14 days post infection...
February 21, 2018: Microbial Pathogenesis
Noriyuki Toji, Katsuo Koshi, Tadashi Furusawa, Toru Takahashi, Toshina Ishiguro-Oonuma, Keiichiro Kizaki, Kazuyoshi Hashizume
Interferon-tau (IFNT) is known as an early pregnancy recognition signal in ruminants. An accurate and convenient IFNT detection system is desirable for the diagnosis of endometrial and trophoblastic functions, including gestation status, in cows. The aim of this study was to develop a new cell-based assay, which involved the stable introduction of an interferon-stimulated gene promoter to a luciferase reporter system. The reactivity of four interferon-stimulated genes to IFNT in Madin-Darby bovine kidney (MDBK) cells was confirmed using reverse transcription-quantitative PCR...
2018: Biomedical Research
Kirby N Swatek, Martina Aumayr, Jonathan N Pruneda, Linda J Visser, Stephen Berryman, Anja F Kueck, Paul P Geurink, Huib Ovaa, Frank J M van Kuppeveld, Tobias J Tuthill, Tim Skern, David Komander
In response to viral infection, cells mount a potent inflammatory response that relies on ISG15 and ubiquitin posttranslational modifications. Many viruses use deubiquitinases and deISGylases that reverse these modifications and antagonize host signaling processes. We here reveal that the leader protease, Lbpro , from foot-and-mouth disease virus (FMDV) targets ISG15 and to a lesser extent, ubiquitin in an unprecedented manner. Unlike canonical deISGylases that hydrolyze the isopeptide linkage after the C-terminal GlyGly motif, Lbpro cleaves the peptide bond preceding the GlyGly motif...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Hiba Ibrahim, Basim Askar, Paul Barrow, Neil Foster
Murine/LPS models of Gram negative sepsis indicate that vasoactive intestinal peptide (VIP) has therapeutic potential. We investigated the unknown effect of VIP on JAK/STAT proteins and genes in human monocytes infected with Salmonella Typhimurium 14028. S. Typhimurium 14028 increased expression of both IL-6 receptor (IL-6R) and interferon gamma receptor 1 (IFNγR1) on monocytes but co-culture of infected monocytes with VIP (10-7 M) only decreased expression of IFNγR1 (P < 0.05). In contrast, S. Typhimurium 14028 infection or co-culture with VIP had no effect on IL-10 receptor expression on the monocyte surface...
February 15, 2018: Cytokine
Wei He, Ying Wei, Jing Yao, Xin Xie, Jiabin Huang, Siyuan Lin, Kang Ouyang, Ying Chen, Weijian Huang, Zuzhang Wei
Previously, a spontaneous 88-amino-acid (aa) deletion in nsp2 was associated with cell-adaptation of porcine reproductive and respiratory syndrome virus (PRRSV) strain JXM100, which arose during passaging of the highly pathogenic PRRSV (HP-PRRSV) strain JX143 in MARC-145 cells. Here, to elucidate the biological role of this deletion, we specifically deleted the region of a cDNA clone of HP-PRRSV strain JX143 (pJX143) corresponding to these 88 amino acids. The effect of the deletion on virus replication in cultured cells and transcriptional activation of inflammatory cytokines and chemokines in pulmonary alveolar macrophages (PAMs) was examined...
February 13, 2018: Archives of Virology
Kenta Jounai, Tetsu Sugimura, Yuji Morita, Konomi Ohshio, Daisuke Fujiwara
Lactococcus lactis subsp. lactis JCM 5805 (LC-Plasma) is a strain of lactic acid bacteria (LAB) that activates murine and human plasmacytoid dendritic cells (pDCs) to express interferons (IFNs). Oral administration of LC-Plasma drastically decreased fatality levels caused by parainfluenza virus infection in a murine model. In this study, we investigated the anti-viral effects of oral administration of LC-Plasma using a suckling mouse model of rhesus rotavirus (RV) infection. LC-Plasma-fed mice showed improvement in retardation of body weight gain, fecal scores, and a reduction in RV titer in the feces when compared to control mice...
January 27, 2018: International Immunopharmacology
Wanwan Zhang, Peng Jia, Wei Liu, Yunlong Li, Meisheng Yi, Kuntong Jia
Tumor necrosis factor receptor-associated factor 3 (TRAF3) is a multifunctional regulator implicated in both bacterial defense and antiviral immunity. Here, a TRAF3 gene from the seawater fish sea perch, designated as LjTRAF3, was characterized. The full-length cDNA of LjTRAF3 was 2972 bp including a 5' untranslated region (UTR) of 243 bp, a 3'UTR of 941 bp and a putative open reading frame of 1608 bp encoding a putative protein of 536 amino acid. The deduced LjTRAF3 protein contained a RING finger, two zinc fingers, a coiled-coil, and a meprin and TRAF-C homology domain...
January 30, 2018: Fish & Shellfish Immunology
Lang Yoo, A-Rum Yoon, Chae-Ok Yun, Kwang Chul Chung
The carboxyl terminus of Hsp70-interacting protein (CHIP) acts as a ubiquitin E3 ligase and a link between the chaperones Hsp70/90 and the proteasome system, playing a vital role in maintaining protein homeostasis. CHIP regulates a number of proteins involved in a myriad of physiological and pathological processes, but the underlying mechanism of action via posttranslational modification has not been extensively explored. In this study, we investigated a novel modulatory mode of CHIP and its effect on CHIP enzymatic activity...
January 24, 2018: Cell Death & Disease
Kyung-Hee Kim, In Jung Yang, Woo-Jin Kim, Choul-Ji Park, Jong-Won Park, Gyeong Eon Noh, Seunghyung Lee, Young Mee Lee, Hyung Kyu Hwang, Hyun Chul Kim
Interferon-stimulated gene 15 (ISG15) is known to interfere with viral replication and infection by limiting the viral infection of cells. Interferon-stimulated gene 15 (ISG15) interferes with viral replication and infectivity by limiting viral infection in cells. It also plays an important role in the immune response. In this study, tissue-specific expression of ISG15 in healthy rock bream samples and spatial and temporal expression analysis of rock bream ISG15 (RbISG15) were performed following rock bream iridovirus (RSIV) infection...
December 2017: Balsaeng'gwa Saengsig
Pang-Kuo Lo, Yuan Yao, Ji Shin Lee, Yongshu Zhang, Weiliang Huang, Maureen A Kane, Qun Zhou
Current understanding of aggressive human basal-like triple-negative breast cancer (TNBC) remains incomplete. In this study, we show endothelial lipase (LIPG) is aberrantly overexpressed in basal-like TNBCs. We demonstrate that LIPG is required for in vivo tumorigenicity and metastasis of TNBC cells. LIPG possesses a lipase-dependent function that supports cancer cell proliferation and a lipase-independent function that promotes invasiveness, stemness and basal/epithelial-mesenchymal transition features of TNBC...
January 19, 2018: ELife
Lisa Maria Mustachio, Yun Lu, Masanori Kawakami, Jason Roszik, Sarah J Freemantle, Xi Liu, Ethan Dmitrovsky
Ubiquitination and ubiquitin-like posttranslational modifications (PTM) regulate activity and stability of oncoproteins and tumor suppressors. This implicates PTMs as antineoplastic targets. One way to alter PTMs is to inhibit activity of deubiquitinases (DUB) that remove ubiquitin or ubiquitin-like proteins from substrate proteins. Roles of DUBs in carcinogenesis have been intensively studied, yet few inhibitors exist. Prior work provides a basis for the ubiquitin-specific protease 18 (USP18) as an antineoplastic target...
January 17, 2018: Cancer Research
L Han, Y Zhang, Q Wang, M Xin, K Yang, K Lei, M Sun
Epstein-Barr (EB) virus infection has long been speculated to evoke systemic lupus erythematosus (SLE). Since a virus infection can induce interferon (IFN) system activation, we aimed to discover the relationship between the two in the progression of SLE in a Chinese inpatient cohort. Methods Peripheral blood mononuclear cells and sera were isolated from 116 SLE patients and 76 healthy controls. Antibodies against EBV-VCA (IgM and IgG) and EBNA (IgG) along with IFNα in patient sera were detected with enzyme-linked immunosorbent assays...
January 1, 2018: Lupus
Myung-Hwa Jung, Chamilani Nikapitiya, Sung-Ju Jung
Rock bream iridovirus (RBIV) causes severe mass mortalities in rock bream (Oplegnathus fasciatus) in Korea. In this study, we investigated the potential of viral membrane protein to induce antiviral status protecting rock bream against RBIV infection. We found that fish administered with ORF008L (myristoylated membrane protein, MMP) vaccine exhibited significantly higher levels of survival compared to ORF007L (major capsid protein, MCP). Moreover, ORF008L-based DNA vaccinated fish showed significant protection at 4 and 8 weeks post vaccination (wpv) than non-vaccinated fish after infected with RBIV (6...
January 8, 2018: Vaccine
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