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https://www.readbyqxmd.com/read/28329286/short-course-tlr9-agonist-treatment-impacts-innate-immunity-and-plasma-viremia-in-individuals-with-hiv-infection
#1
Line Vibholm, Mariane H Schleimann, Jesper F Højen, Thomas Benfield, Rasmus Offersen, Katrine Rasmussen, Rikke Olesen, Anders Dige, Jørgen Agnholt, Judith Grau, Maria Buzon, Burghardt Wittig, Mathias Lichterfeld, Andreas Munk Petersen, Xutao Deng, Mohammed Abdel-Mohsen, Satish K Pillai, Sofie Rutsaert, Wim Trypsteen, Ward De Spiegelaere, Linos Vandekerchove, Lars Østergaard, Thomas A Rasmussen, Paul W Denton, Martin Tolstrup, Ole S Søgaard
Background: Treatment with latency reversing agents (LRA) enhances HIV-1 transcription in vivo but only leads to modest reductions in the size of the reservoir, possibly due to insufficient immune-mediated elimination of infected cells. We hypothesized that a single drug molecule - a novel toll-like receptor 9 (TLR9) agonist, MGN1703 - could function as an enhancer of innate immunity and an LRA in vivo. Methods: We conducted a single-arm, open-label study, where 15 virologically suppressed HIV-1 infected individuals on antiretroviral therapy received 60 mg MGN1703 s...
March 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28328794/hcv-drives-increased-type-i-ifn-associated-impairments-associated-to-fibrosis-severity-in-art-treated-hiv-1-hcv-coinfected-individuals
#2
Morgane Griesbeck, Marc-Antoine Valantin, Karine Lacombe, Assia Samri-Hassimi, Julie Bottero, Catherine Blanc, Zineb Sbihi, Rima Zoorob, Christine Katlama, Marguerite Guiguet, Marcus Altfeld, Brigitte Autran
BACKGROUND: Viral coinfections might contribute to the increased immune activation and inflammation that persist in ART-treated HIV-1 patients. We investigated whether the HCV co-infection contributes to such alterations by impairing the pDC IFNα/TLR7 pathway in a highly homogeneous group of ART-treated HIV-1-HCV co-infected patients. METHODS: Twenty nine HIV-1-infected patients with fully suppressive ART were included, fifteen of whom being HCV co-infected with mild to moderate fibrosis and matched for their HIV-1 disease, and thirteen control healthy donors...
March 21, 2017: AIDS
https://www.readbyqxmd.com/read/28287327/mechanism-of-cell-intrinsic-adaptation-to-adams-oliver-syndrome-gene-dock6-disruption-highlights-ubiquitin-like-modifier-isg15-as-a-regulator-of-rho-gtpases
#3
Berati Cerikan, Elmar Schiebel
DOCK6 is a RAC1/CDC42 guanine nucleotide exchange factor, however, little is known about its function and sub-cellular localization. DOCK6 regulates the balance between RAC1 and RHOA activity during cell adhesion and is important for CDC42-dependent mitotic chromosome alignment. Surprisingly, a cell intrinsic adaptation mechanism compensates for errors in these DOCK6 functions that arise as a consequence of prolonged DOCK6 depletion or complete removal in DOCK6 knockout cells. Down-regulation of the ubiquitin-like modifier ISG15 accounts for this adaptation...
February 23, 2017: Small GTPases
https://www.readbyqxmd.com/read/28285335/cell-type-dependent-regulation-of-free-isg15-levels-and-isgylation
#4
Angeles C Tecalco Cruz, Karen Mejía-Barreto
Interferon-stimulated gene 15 (ISG15) is an ubiquitin-like protein, which can either be found as a free protein or covalently-bound to target proteins via ISGylation. The functions of free and conjugated ISG15 are ambiguous in tumorigenesis owing to its roles as an oncogene and a tumour suppressor gene. This dual role for ISG15 could be a result of the cancer cell type and the cellular context. Here, we report that ISG15 expression is upregulated in different cancer cells compared to normal cells. Furthermore, we found higher endogenous, free ISG15 protein levels in MCF7 breast cancer cells than in other cells, suggesting that non-conjugated ISG15 levels are cell type-specific...
March 11, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28284594/orally-administered-live-attenuated-salmonella-typhimurium-protects-mice-against-lethal-infection-with-h1n1-influenza-virus
#5
Nitin Machindra Kamble, Irshad Ahmed Hajam, John Hwa Lee
Pre-stimulation of toll-like receptors (TLRs) by agonists has been shown to increase protection against influenza virus infection. In this study, we evaluated the protective response generated against influenza A/Puerto Rico/8/1934 (PR8; H1N1) virus by oral and nasal administration of live attenuated Salmonella enterica serovar Typhimurium, JOL911 strain, in mice. Oral and nasal inoculation of JOL911 significantly increased the mRNA copy number of TLR-2, TLR4 and TLR5, and downstream type I interferon (IFN) molecules, IFN-α and IFN-β, both in peripheral blood mononuclear cells (PBMCs) and in lung tissue...
March 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28279792/transcriptome-data-analysis-of-grass-carp-ctenopharyngodon-idella-infected-by-reovirus-provides-insights-into-two-immune-related-genes
#6
Zao Dai, Jicheng Li, Chengyu Hu, Fang Wang, Binhua Wang, Xiao Shi, Qunhao Hou, Waigen Huang, Gang Lin
Grass carp (Ctenopharyngodon idella) was one of the economically important freshwater fish in China. However, hemorrhagic disease caused by grass carp reovirus (GCRV) results in a tremendous loss in the process of grass carp cultivation. Transcriptome analysis could provide a comprehensive understanding of the molecular mechanisms involved in specific biological processes and diseases for the resistance to reovirus infection of grass carp. In this study, the raw data from NCBI (accession number: SRA099702) were analyzed, in which, 50 significant differentially expressed genes by routine transcriptome analysis and 84 notably differentially expressed genes by co-expression network method...
March 6, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28254416/molecular-characterization-and-biological-activity-of-bovine-interferon-omega3
#7
Dong An, Yongli Guo, Jun Bao, Xiuxin Luo, Ying Liu, Bo Ma, Mingchun Gao, Junwei Wang
Bovine interferon-omega3 (BoIFN-ω3) gene was amplified from bovine liver genomic DNA, which encodes a 195-amino acid protein containing a 23-amino acid signal peptide. Analysis of the molecular characteristics revealed that BoIFN-ω3 evolving from IFN-ω, contained four cysteine residues and five alpha helices, showing that BoIFN-ω3 presented the typical molecular characteristics of type I interferon. BoIFN-ω3 exhibited antiviral and antiproliferative activities, which exerted a protective effect against VSV in several mammalian cell lines, as well as against BEV, IBRV, and BVDV in MDBK cell...
February 10, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28242811/deubiquitinase-usp18-loss-mislocalizes-and-destabilizes-kras-in-lung-cancer
#8
Lisa Maria Mustachio, Yun Lu, Laura J Tafe, Vincent Memoli, Jaime Rodriguez-Canales, Barbara Mino, Pamela Andrea Villalobos, Ignacio Wistuba, Hiroyuki Katayama, Samir M Hanash, Jason Roszik, Masanori Kawakami, Kwang-Jin Cho, John F Hancock, Fadzai Chinyengetere, Shanhu Hu, Xi Liu, Sarah J Freemantle, Ethan Dmitrovsky
KRAS is frequently mutated in lung cancers and is associated with aggressive biology and chemotherapy resistance. Therefore, innovative approaches are needed to treat these lung cancers. Prior work implicated the interferon-stimulated gene 15 (ISG15) deubiquitinase (DUB) USP18 as having anti-neoplastic activity by regulating lung cancer growth and oncoprotein stability. This study demonstrates that USP18 affects the stability of the KRAS oncoprotein. Interestingly, loss of USP18 reduced KRAS expression and engineered gain of USP18 expression increased KRAS protein levels in lung cancer cells...
February 27, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28241406/interferon-stimulated-gene-15-in-the-control-of-cellular-responses-to-genotoxic-stress
#9
REVIEW
Young Joo Jeon, Jong Ho Park, Chin Ha Chung
Error-free replication and repair of DNA are pivotal to organisms for faithful transmission of their genetic information. Cells orchestrate complex signaling networks that sense and resolve DNA damage. Post-translational protein modifications by ubiquitin and ubiquitin-like proteins, including SUMO and NEDD8, are critically involved in DNA damage response (DDR) and DNA damage tolerance (DDT). The expression of interferon-stimulated gene 15 (ISG15), the first identified ubiquitin-like protein, has recently been shown to be induced under various DNA damage conditions, such as exposure to UV, camptothecin, and doxorubicin...
February 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28239662/zika-virus-infects-cells-lining-the-blood-retinal-barrier-and-causes-chorioretinal-atrophy-in-mouse-eyes
#10
Pawan Kumar Singh, John-Michael Guest, Mamta Kanwar, Joseph Boss, Nan Gao, Mark S Juzych, Gary W Abrams, Fu-Shin Yu, Ashok Kumar
Zika virus (ZIKV) is an important pathogen that causes not only neurologic, but also ocular, abnormalities. Thus, it is imperative that models to study ZIKV pathogenesis in the eye are developed to identify potential targets for interventions. Here, we studied ZIKV interactions with human retinal cells and evaluated ZIKV's pathobiology in mouse eyes. We showed that cells lining the blood-retinal barrier (BRB), the retinal endothelium, and retinal pigment epithelium (RPE) were highly permissive and susceptible to ZIKV-induced cell death...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28239027/estrous-cycle-stage-dependent-manner-of-type-i-interferon-stimulated-genes-induction-in-the-bovine-endometrium
#11
Takahiro Shirozu, Hiroki Iwano, Takatoshi Ogiso, Toshiyuki Suzuki, Ahmed Z Balboula, Hanako Bai, Manabu Kawahara, Koji Kimura, Hitomi Takahashi, Bai Rulan, Sung-Woo Kim, Yojiro Yanagawa, Masashi Nagano, Kazuhiko Imakawa, Masashi Takahashi
Interferon tau (IFN-τ) is a ruminant-specific type I IFN secreted by a conceptus before its attachment to the uterus. IFN-τ induces the expression of IFN-stimulated genes (ISGs) via the type I IFN receptor (IFNAR), which is composed of IFNAR1 and IFNAR2 subunits in the endometrium. However, expression patterns of IFNARs during the estrous cycle have not been reported. We hypothesized that the response to a type I IFN changes along with IFNARs and the IFN-regulatory factors (IRFs) driving transcription of IFN signal-related genes and modulating a type I IFN signal during the estrous cycle...
February 26, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28212619/brain-and-liver-pathology-amyloid-deposition-and-interferon-responses-among-older-hiv-positive-patients-in-the-late-haart-era
#12
Isaac H Solomon, Umberto De Girolami, Sukrutha Chettimada, Vikas Misra, Elyse J Singer, Dana Gabuzda
BACKGROUND: HIV+ patients on highly active antiretroviral therapy (HAART) with suppressed viral loads have a low incidence of HIV-associated dementia, but increased prevalence of milder forms of HIV-associated neurocognitive disorders (HAND). These milder forms of HAND are often associated with minimal histological abnormalities, and their pathophysiology is unclear. Comorbidities, altered amyloid metabolism, accelerated brain aging, and activated interferon responses are suspected to play a role in HAND pathogenesis in HAART-treated persons...
February 17, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28204879/interferon-stimulated-gene-15-expression-in-systemic-lupus-erythematosus-diagnostic-value-and-association-with-lymphocytopenia
#13
Y Yuan, H Ma, Z Ye, W Jing, Z Jiang
BACKGROUND: The aim of this study was to (a) assess the relationship between interferon-stimulated gene 15 (ISG15) expression and clinical manifestations of systemic lupus erythematosus (SLE) and (b) investigate the diagnostic value of ISG15 in SLE. PATIENTS AND METHODS: The study comprised 28 patients newly diagnosed with SLE, 10 patients with undifferentiated connective tissue disease, and 22 healthy volunteers. Of the SLE patients, 14 were chosen randomly to be followed up for 4 weeks...
February 15, 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/28202760/restriction-of-hcmv-replication-by-isg15-a-host-effector-regulated-by-cgas-sting-dsdna-sensing
#14
Christopher Bianco, Ian Mohr
Accumulation of the interferon-stimulated gene (ISG) 15 protein product, which is reversibly conjugated to numerous polypeptide targets, impacts the proteome and physiology of uninfected and infected cells. While many viruses, including human cytomegalovirus (HCMV) blunt host antiviral defenses by limiting ISG expression, the overall abundance of ISG15 monomer and protein conjugates rises in HCMV-infected cells. However, the molecular signals underlying ISG15 accumulation and whether the ISG15 polypeptide itself influences HCMV infection biology remain unknown...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28186990/ube2l6-ubch8-and-isg15-attenuate-autophagy-in-esophageal-cancer-cells
#15
Chloe M Falvey, Tracey R O'Donovan, Shereen El-Mashed, Michelle J Nyhan, Seamus O'Reilly, Sharon L McKenna
Esophageal cancer remains a poor prognosis cancer due to advanced stage of presentation and drug resistant disease. To understand the molecular mechanisms influencing response to chemotherapy, we examined genes that are differentially expressed between drug sensitive, apoptosis competent esophageal cancer cells (OE21, OE33, FLO-1) and those which are more resistant and do not exhibit apoptosis (KYSE450 and OE19). Members of the ISG15 (ubiquitin-like) protein modification pathway, including UBE2L6 and ISG15, were found to be more highly expressed in the drug sensitive cell lines...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28165509/structural-basis-of-the-specificity-of-usp18-toward-isg15
#16
Anja Basters, Paul P Geurink, Annika Röcker, Katharina F Witting, Roya Tadayon, Sandra Hess, Marta S Semrau, Paola Storici, Huib Ovaa, Klaus-Peter Knobeloch, Günter Fritz
Protein modification by ubiquitin and ubiquitin-like modifiers (Ubls) is counteracted by ubiquitin proteases and Ubl proteases, collectively termed DUBs. In contrast to other proteases of the ubiquitin-specific protease (USP) family, USP18 shows no reactivity toward ubiquitin but specifically deconjugates the interferon-induced Ubl ISG15. To identify the molecular determinants of this specificity, we solved the crystal structures of mouse USP18 alone and in complex with mouse ISG15. USP18 was crystallized in an open and a closed conformation, thus revealing high flexibility of the enzyme...
February 6, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28143523/immune-and-biochemical-responses-in-skin-differ-between-bovine-hosts-genetically-susceptible-and-resistant-to-the-cattle-tick-rhipicephalus-microplus
#17
Alessandra Mara Franzin, Sandra Regina Maruyama, Gustavo Rocha Garcia, Rosane Pereira Oliveira, José Marcos Chaves Ribeiro, Richard Bishop, Antônio Augusto Mendes Maia, Daniela Dantas Moré, Beatriz Rossetti Ferreira, Isabel Kinney Ferreira de Miranda Santos
BACKGROUND: Ticks attach to and penetrate their hosts' skin and inactivate multiple components of host responses in order to acquire a blood meal. Infestation loads with the cattle tick, Rhipicephalus microplus, are heritable: some breeds carry high loads of reproductively successful ticks, whereas in others, few ticks feed and reproduce efficiently. METHODS: In order to elucidate the mechanisms that result in the different outcomes of infestations with cattle ticks, we examined global gene expression and inflammation induced by tick bites in skins from one resistant and one susceptible breed of cattle that underwent primary infestations with larvae and nymphs of R...
January 31, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28109912/ifn-lambda-preferably-inhibits-pedv-infection-of-porcine-intestinal-epithelial-cells-compared-with-ifn-alpha
#18
Lin Li, Fang Fu, Mei Xue, Weiye Chen, Jin Liu, Hongyan Shi, Jianfei Chen, Zhigao Bu, Li Feng, Pinghuang Liu
In contrast to type I interferons that target various types of cells and organs, interferon lambda (IFN-L) primarily acts on mucosal epithelial cells and exhibits robust antiviral activity within the mucosal surface. Porcine epidemic diarrhea virus (PEDV), which causes high morbidity and mortality in piglets, is an enteropathogenic coronavirus with economic importance. Here, we demonstrated that both recombinant porcine IFN-L1 (rpIFN-L1) and rpIFN-L3 have powerful antiviral activity against PEDV infection of both Vero E6 cells and the intestinal porcine epithelial cell line J2 (IPEC-J2)...
April 2017: Antiviral Research
https://www.readbyqxmd.com/read/28087453/the-impact-of-isgylation-during-mycobacterium-tuberculosis-infection-in-mice
#19
Jacqueline M Kimmey, Jessica A Campbell, Leslie A Weiss, Kristen J Monte, Deborah J Lenschow, Christina L Stallings
Mycobacterium tuberculosis infection results in 1.5 million deaths annually. Type I interferon (IFN) signaling through its receptor IFNAR correlates with increased severity of disease, although how this increases susceptibility to M. tuberculosis remains uncertain. ISG15 is one of the most highly induced interferon stimulated genes (ISGs) during M. tuberculosis infection. ISG15 functions by conjugation to target proteins (ISGylation), by noncovalent association with intracellular proteins, and by release from the cell...
January 10, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/28060952/trim25-enhances-the-antiviral-action-of-zinc-finger-antiviral-protein-zap
#20
Melody M H Li, Zerlina Lau, Pamela Cheung, Eduardo G Aguilar, William M Schneider, Leonia Bozzacco, Henrik Molina, Eugen Buehler, Akinori Takaoka, Charles M Rice, Dan P Felsenfeld, Margaret R MacDonald
The host factor and interferon (IFN)-stimulated gene (ISG) product, zinc-finger antiviral protein (ZAP), inhibits a number of diverse viruses by usurping and intersecting with multiple cellular pathways. To elucidate its antiviral mechanism, we perform a loss-of-function genome-wide RNAi screen to identify cellular cofactors required for ZAP antiviral activity against the prototype alphavirus, Sindbis virus (SINV). In order to exclude off-target effects, we carry out stringent confirmatory assays to verify the top hits...
January 2017: PLoS Pathogens
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