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https://www.readbyqxmd.com/read/28630501/ifn-%C3%AE-4-potently-blocks-ifn-%C3%AE-signalling-by-isg15-and-usp18-in-hepatitis-c-virus-infection
#1
Pil Soo Sung, Seon-Hui Hong, Jae-Hee Chung, Sojeong Kim, Su-Hyung Park, Ho Min Kim, Seung Kew Yoon, Eui-Cheol Shin
Genetic polymorphisms in IFNL4 have been shown to predict responses to IFN-α-based therapy in hepatitis C virus (HCV)-infected patients. The IFNL4-ΔG genotype, which encodes functional IFN-λ4 protein, is associated with a poor treatment response. In the present study, we investigated the induction and biological effects of IFN-λ4 in HCV-infected hepatocytes and their association with responsiveness to IFN-α. We also studied the effects of direct-acting antiviral (DAA) treatment on IFN-λ4 expression and IFN-α responsiveness...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28605413/acute-bovine-viral-diarrhoea-virus-infection-inhibits-expression-of-interferon-tau-stimulated-genes-in-bovine-endometrium
#2
Zhangrui Cheng, Latta Chauhan, Amy Teresa Barry, Ayimuguli Abudureyimu, Chike F Oguejiofor, Xing Chen, D Claire Wathes
Bovine viral diarrhoea virus (BVDV) can evade host detection by down-regulation of interferon signalling pathways. Infection of cows with non-cytopathic (ncp) BVDV can cause early embryonic mortality. Upregulation of type I interferon stimulated genes (ISGs) by blastocyst-secreted interferon tau (IFNT) is a crucial component of the maternal recognition of pregnancy (MRP) in ruminants. This study investigated the potential of acute BVDV infection to disrupt MRP by modulating endometrial ISG expression. Endometrial cells from 10 BVDV-free cows were cultured and treated with 0 or 100 ng/ml IFNT for 24 h in the absence or presence of ncpBVDV infection to yield 4 treatment groups: CONT, ncpBVDV, IFNT or ncpBVDV+IFNT...
June 12, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28602740/protective-immunity-against-rock-bream-iridovirus-rbiv-infection-and-tlr3-mediated-type-i-interferon-signaling-pathway-in-rock-bream-oplegnathus-fasciatus-following-poly-i-c-administration
#3
Myung-Hwa Jung, Sung-Ju Jung
In this study, we evaluated the potential of poly (I:C) to induce antiviral status for protecting rock bream from RBIV infection. Rock bream injected with poly (I:C) at 2 days before infection (1.1 × 10(4)) at 20 °C had significantly higher protection with RPS 13.4% and 33.4% at 100 and 200 μg/fish, respectively, through 100 days post infection (dpi). The addition of boost immunization with poly (I:C) at before/post infection at 20 °C clearly enhanced the level of protection showing 33.4% and 60.0% at 100 and 200 μg/fish, respectively...
June 8, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28599020/isg15-in-host-defense-against-candida-albicans-infection-in-a-mouse-model-of-fungal-keratitis
#4
Chen Dong, Nan Gao, Bing X Ross, Fu-Shin X Yu
Purpose: ISG15, a di-ubiquitin-like protein, is critical for controlling certain viral and bacterial infections. We sought to determine if ISG15 plays a role in corneal innate immunity against Candida albicans (C. albicans) using a C57BL/6 (B6) mouse model of human fungal keratitis. Methods: Scarified corneas of adult B6 mice were pretreated with TLR5 ligand flagellin and then inoculated with C. albicans. The expression of ISG15 and other genes involved in ISG15 conjugation (ISGylation) was determined by real-time PCR...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28588308/a-four-biomarker-blood-signature-discriminates-systemic-inflammation-due-to-viral-infection-versus-other-etiologies
#5
D L Sampson, B A Fox, T D Yager, S Bhide, S Cermelli, L C McHugh, T A Seldon, R A Brandon, E Sullivan, J J Zimmerman, M Noursadeghi, R B Brandon
The innate immune system of humans and other mammals responds to pathogen-associated molecular patterns (PAMPs) that are conserved across broad classes of infectious agents such as bacteria and viruses. We hypothesized that a blood-based transcriptional signature could be discovered indicating a host systemic response to viral infection. Previous work identified host transcriptional signatures to individual viruses including influenza, respiratory syncytial virus and dengue, but the generality of these signatures across all viral infection types has not been established...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28543875/unconjugated-interferon-stimulated-gene-15-specifically-interacts-with-the-hepatitis-c-virus-ns5a-protein-via-domain-i
#6
Nanae Minami, Takayuki Abe, Lin Deng, Chieko Matsui, Takasuke Fukuhara, Yoshiharu Matsuura, Ikuo Shoji
Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein induced by type I interferon. Although several groups have reported ISGylation of the HCV NS5A protein, it is still unclear whether ISGylation of NS5A has anti-viral or pro-viral effects in HCV infection. In the present study, we examined the role of ISGylation-independent, unconjugated ISG15 in HCV infection. Immunoprecipitation analyses revealed that ISG15 specifically interacted with NS5A domain I. The ISG15 mutants lacking a C-terminal glycine residue essential for ISGylation still interacted with NS5A protein...
May 25, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28542609/potent-and-selective-inhibition-of-pathogenic-viruses-by-engineered-ubiquitin-variants
#7
Wei Zhang, Ben A Bailey-Elkin, Robert C M Knaap, Baldeep Khare, Tim J Dalebout, Garrett G Johnson, Puck B van Kasteren, Nigel J McLeish, Jun Gu, Wenguang He, Marjolein Kikkert, Brian L Mark, Sachdev S Sidhu
The recent Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola and Zika virus outbreaks exemplify the continued threat of (re-)emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. Many viruses, including MERS-CoV and the Crimean-Congo hemorrhagic fever virus (CCHFV) encode deubiquitinating (DUB) enzymes that are critical for viral replication and pathogenicity. They bind and remove ubiquitin (Ub) and interferon stimulated gene 15 (ISG15) from cellular proteins to suppress host antiviral innate immune responses...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28535250/evidence-for-the-deregulation-of-protein-turnover-pathways-in-atm-deficient-mouse-cerebellum-an-organotypic-study
#8
Catherine D Kim, Ryan E Reed, Meredith A Juncker, Zhide Fang, Shyamal D Desai
Interferon-stimulated gene 15 (ISG15), an antagonist of the ubiquitin pathway, is elevated in cells and brain tissues obtained from ataxia telangiectasia (A-T) patients. Previous studies reveal that an elevated ISG15 pathway inhibits ubiquitin-dependent protein degradation, leading to activation of basal autophagy as a compensatory mechanism for protein turnover in A-T cells. Also, genotoxic stress (ultraviolet [UV] radiation) deregulates autophagy and induces aberrant degradation of ubiquitylated proteins in A-T cells...
May 23, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28532450/lps-induced-systemic-inflammation-reveals-an-immunomodulatory-role-for-the-prion-protein-at-the-blood-brain-interface
#9
Ø Salvesen, M R Reiten, A Espenes, M K Bakkebø, M A Tranulis, C Ersdal
BACKGROUND: The cellular prion protein (PrP(C)) is an evolutionary conserved protein abundantly expressed not only in the central nervous system but also peripherally including the immune system. A line of Norwegian dairy goats naturally devoid of PrP(C) (PRNP (Ter/Ter)) provides a novel model for studying PrP(C) physiology. METHODS: In order to explore putative roles for PrP(C) in acute inflammatory responses, we performed a lipopolysaccharide (LPS, Escherichia coli O26:B6) challenge of 16 goats (8 PRNP (+/+) and 8 PRNP (Ter/Ter)) and included 10 saline-treated controls (5 of each PRNP genotype)...
May 22, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28527896/molecular-characterization-and-expression-analyses-of-the-solea-senegalensis-interferon-stimulated-gene-15-isg15-following-nnv-infections
#10
Daniel Álvarez-Torres, Ana María Podadera, M Carmen Alonso, Isabel Bandín, Julia Béjar, Esther García-Rosado
Interferons are essential in fish resistance to viral infections. They induce interferon-stimulated genes, such as isg15. In this study, the Senegalese sole isg15 gene (ssisg15) has been characterized. As other isg15, ssisg15 contains a 402-bp intron sited in the 5'-UTR, and the full length cDNA is 1492-bp, including a 480-bp ORF. The expression analyses revealed basal levels of isg15 transcripts, and a clear induction after poly I:C injection, that reached maximum values in brain, head kidney and gills. The ssisg15 induction patterns were similar in RGNNV- and SJNNV-inoculated fish, whereas the reassortant (RG/SJ) isolate, which has higher replication fitness, triggered delayed but higher transcript levels...
May 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28521627/disseminated-bacillus-calmette-gu%C3%A3-rin-osteomyelitis-in-twin-sisters-related-to-stat1-gene-deficiency
#11
Sabah Boudjemaa, Linda Dainese, Sébastien Héritier, Caroline Masserot, Samia Hachemane, Jean-Laurent Casanova, Aurore Coulomb, Jacinta Bustamante
Mendelian susceptibility to mycobacterial disease is a rare syndrome characterized by severe clinical infections usually caused by weakly virulent mycobacterial species such as Bacillus Calmette-Guérin vaccines and environmental nontuberculous mycobacteria or more virulent mycobacteria as mycobacterium tuberculosis. Since 1996, 9 genes including 7 autosomal ( STAT1, IFNGR1, IFNGR2, IL12B, IL12RB1, ISG15, and IRF8) and 2 X-linked genes ( NEMO and CYBB) have been identified. Allelic heterogeneity leaded to recognize about 18 genetic diseases with variable clinical phenotypes, but sharing a same physiological mechanism represented by a defect in human IL-12-dependant-INF-γ-mediated immunity...
June 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28492391/hepatitis-c-virus-drives-increased-type-i-interferon-associated-impairments-associated-with-fibrosis-severity-in-antiretroviral-treatment-treated-hiv-1-hepatitis-c-virus-coinfected-individuals
#12
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 antiretroviral treatment (ART)-treated HIV-1 patients. We investigated whether the hepatitis C virus (HCV) coinfection contributes to such alterations by impairing the plasmacytoid dendritic cell (pDC) IFNα/TLR7 pathway in a highly homogeneous group of ART-treated HIV-1-HCV-coinfected patients. METHODS: Twenty-nine HIV-1-infected patients with fully suppressive ART were included, 15 of whom being HCV-coinfected with mild-to-moderate fibrosis and matched for their HIV-1 disease, and 13 control healthy donors...
June 1, 2017: AIDS
https://www.readbyqxmd.com/read/28467275/beyond-isglylation-functions-of-free-intracellular-and-extracellular-isg15
#13
Paula Fernandes Dos Santos, Daniel Santos Mansur
ISG15 is a ubiquitin-like type I IFN-stimulated protein of 15 kDa and is one of the most prominently expressed proteins in viral infections. ISG15 is widely known to be involved in a process called ISGylation, where it binds to over 150 targets from a variety of classes of proteins including central immune signaling pathways such as those mediated by NFκB, JNK, and IRF-3. However, ISG15 also exists in a free form that can act intra- or extracellularly. In vitro and in vivo evidences suggest that free ISG15 play different roles in several cellular processes, from cancer and defense against viral infections to activation of immune cells such as lymphocytes, monocytes, and NK cells...
June 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28438633/structural-insights-into-the-interaction-of-coronavirus-papain-like-proteases-and-interferon-stimulated-gene-product-15-from-different-species
#14
Courtney M Daczkowski, John V Dzimianski, Jozlyn R Clasman, Octavia Goodwin, Andrew D Mesecar, Scott D Pegan
Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) encode multifunctional papain-like proteases (PLPs) that have the ability to process the viral polyprotein to facilitate RNA replication and antagonize the host innate immune response. The latter function involves reversing the post-translational modification of cellular proteins conjugated with either ubiquitin (Ub) or Ub-like interferon-stimulated gene product 15 (ISG15). Ub is known to be highly conserved among eukaryotes, but surprisingly, ISG15 is highly divergent among animals...
April 21, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28423001/pre-hatching-embryo-dependent-and-independent-programming-of-endometrial-function-in-cattle
#15
Mariana Sponchiado, Nathália Souza Gomes, Patrícia Kubo Fontes, Thiago Martins, Maite Del Collado, Athos de Assumpção Pastore, Guilherme Pugliesi, Marcelo Fábio Gouveia Nogueira, Mario Binelli
The bovine pre-implantation embryo secretes bioactive molecules from early development stages, but effects on endometrial function are reported to start only after elongation. Here, we interrogated spatially defined regions of the endometrium transcriptome for responses to a day 7 embryo in vivo. We hypothesize that exposure to an embryo changes the abundance of specific transcripts in the cranial region of the pregnant uterine horn. Endometrium was collected from the uterotubal junction (UTJ), anterior (IA), medial (IM) and posterior (IP) regions of the uterine horn ipsilateral to the CL 7 days after estrus from sham-inseminated (Con) or artificially inseminated, confirmed pregnant (Preg) cows...
2017: PloS One
https://www.readbyqxmd.com/read/28387595/interferon-stimulated-gene-expression-as-a-preferred-biomarker-for-disease-activity-in-aicardi-gouti%C3%A3-res-syndrome
#16
Ben X Wang, Stephanie A Grover, Peter Kannu, Grace Yoon, Ronald M Laxer, E Ann Yeh, Eleanor N Fish
Aicardi-Goutières syndrome (AGS) is an early-onset, genetic disease characterized by recurrent fever, multifocal lesions of the brain, and systemic autoimmunity. We report on 3 AGS patients, 2 siblings with an RNASEH2A gene mutation and 1 patient with a SAMHD1 gene mutation. Serial analysis of peripheral blood from all 3 AGS patients showed consistently elevated expression of the interferon-stimulated genes (ISGs): ISG15, RSAD2, and IFI27, not observed in unaffected family members. Enumeration of circulating white blood cells and platelets and examination of C-reactive protein showed no significant deviation from the normal range for Patient 2 with the RNASEH2A mutation and Patient 3 with the SAMHD1 mutation, even when Patient 2 had magnetic resonance imaging abnormalities and ongoing febrile episodes...
April 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28373872/type-i-interferon-gene-response-is-increased-in-early-and-established-rheumatoid-arthritis-and-correlates-with-autoantibody-production
#17
Julio E Castañeda-Delgado, Yadira Bastián-Hernandez, Noe Macias-Segura, David Santiago-Algarra, Jose D Castillo-Ortiz, Ana L Alemán-Navarro, Pedro Martínez-Tejada, Leonor Enciso-Moreno, Yolanda Garcia-De Lira, Diana Olguín-Calderón, Leendert A Trouw, Cesar Ramos-Remus, Jose A Enciso-Moreno
BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory debilitating disease that affects the joints in the early and productive phases of an individual's life. Several cytokines have been linked to the disease pathogenesis and are known to contribute to the inflammatory state characteristic of RA. The participation of type I interferon (IFN) in the pathogenesis of the disease has been already described as well as the identity of the genes that are regulated by this molecule, which are collectively known as the type I IFN signature...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28362325/possible-roles-of-cc-and-cxc-chemokines-in-regulating-bovine-endometrial-function-during-early-pregnancy
#18
Ryosuke Sakumoto, Ken-Go Hayashi, Shiori Fujii, Hiroko Kanahara, Misa Hosoe, Tadashi Furusawa, Keiichiro Kizaki
The aim of the present study was to determine the possible roles of chemokines in regulating bovine endometrial function during early pregnancy. The expression of six chemokines, including CCL2, CCL8, CCL11, CCL14, CCL16, and CXCL10, was higher in the endometrium at 15 and 18 days of pregnancy than at the same days in non-pregnant animals. Immunohistochemical staining showed that chemokine receptors (CCR1, CCR2, CCR3, and CXCR3) were expressed in the epithelial cells and glandular epithelial cells of the bovine endometrium as well as in the fetal trophoblast obtained from a cow on day 18 of pregnancy...
March 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28348873/molecular-and-biochemical-characterization-of-the-ns1-protein-of-non-cultured-influenza-b-virus-strains-circulating-in-singapore
#19
Muhammad Raihan Jumat, Puisan Wong, Raphael Tze Chuen Lee, Sebastian Maurer-Stroh, Boon Huan Tan, Richard J Sugrue
In this study we compared the NS1 protein of Influenza B/Lee/40 and several non-cultured Influenza B virus clinical strains detected in Singapore. In B/Lee/40 virus-infected cells and in cells expressing the recombinant B/Lee/40 NS1 protein a full-length 35 kDa NS1 protein and a 23 kDa NS1 protein species (p23) were detected. Mutational analysis of the NS1 gene indicated that p23 was generated by a novel cleavage event within the linker domain between an aspartic acid and proline at amino acid residues at positions 92 and 93 respectively (DP92-93), and that p23 contained the first 92 amino acids of the NS1 protein...
August 2016: Microbial Genomics
https://www.readbyqxmd.com/read/28329286/short-course-toll-like-receptor-9-agonist-treatment-impacts-innate-immunity-and-plasma-viremia-in-individuals-with-human-immunodeficiency-virus-infection
#20
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, Mohamed 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 (LRAs) enhances human immunodeficiency virus type 1 (HIV-1) transcription in vivo but leads to only 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 in which 15 virologically suppressed HIV-1-infected individuals on antiretroviral therapy received 60 mg MGN1703 subcutaneously twice weekly for 4 weeks...
June 15, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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