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ISG15

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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)...
January 19, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28087453/the-impact-of-isgylation-during-mycobacterium-tuberculosis-infection-in-mice
#8
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
#9
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
https://www.readbyqxmd.com/read/28046052/integrative-analysis-of-immunological-data-to-explore-chronic-immune-t-cell-activation-in-successfully-treated-hiv-patients
#10
Marie-Quitterie Picat, Isabelle Pellegrin, Juliette Bitard, Linda Wittkop, Cécile Proust-Lima, Benoît Liquet, Jean-François Moreau, Fabrice Bonnet, Patrick Blanco, Rodolphe Thiébaut
OBJECTIVES: To unravel the complex relationships between cytomegalovirus-induced-, autoimmune-induced responses, microbial translocation and chronic immune activation (CIA) in successfully treated HIV-infected patients and to explore the mediating role of alpha-interferon in these processes. DESIGN: Cross-sectional study nested in the ANRS CO3 Aquitaine Cohort, a prospective hospital-based cohort of HIV-1-infected patients in South-Western France. METHODS: Patients initiated antiretroviral therapy between 2005 and 2008 and were treated with sustained virological suppression for at least two years...
2017: PloS One
https://www.readbyqxmd.com/read/28043874/intrahepatic-innate-immune-response-pathways-are-downregulated-in-untreated-chronic-hepatitis-b-patients
#11
Fanny Lebossé, Barbara Testoni, Judith Fresquet, Floriana Facchetti, Enrico Galmozzi, Maëlenn Fournier, Valérie Hervieu, Pascale Berthillon, Françoise Berby, Isabelle Bordes, David Durantel, Massimo Levrero, Pietro Lampertico, Fabien Zoulim
BACKGROUND & AIMS: Hepatitis B virus (HBV) persistence and the pathobiology of chronic HBV (CHB) infections result from the interplay between viral replication and host immune responses. We aimed to comprehensively analyse the expression of intrahepatic host genes as well as serum and liver HBV markers in a large cohort of untreated CHB patients. METHODS: One-hundred and five CHB patients untreated at the time of liver biopsy (34 HBeAg[+] and 71 HBeAg[-]) were analysed for the intrahepatic expression profile of 67 genes belonging to multiple innate immunity pathways...
December 30, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/28036111/hepatic-ifnl4-expression-is-associated-with-non-response-to-interferon-based-therapy-through-the-regulation-of-basal-interferon-stimulated-gene-expression-in-chronic-hepatitis-c-patients
#12
Miyako Murakawa, Yasuhiro Asahina, Fukiko Kawai-Kitahata, Mina Nakagawa, Sayuri Nitta, Satoshi Otani, Hiroko Nagata, Shun Kaneko, Yu Asano, Tomoyuki Tsunoda, Masato Miyoshi, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Yasuhito Tanaka, Sayuki Iijima, Kaoru Tsuchiya, Namiki Izumi, Shuju Tohda, Mamoru Watanabe
Single nucleotide polymorphisms (SNPs) within or near interferon lambda 4 (IFNL4) gene located upstream of IFNL3 are associated with response to anti-HCV therapy both in interferon (IFN)-based and IFN-free regimens. IFNL4 encodes IFNλ4, a newly discovered type III IFN, and its expression is controlled by rs368234815-TT/ΔG, which is in strong linkage disequilibrium (LD) with other tag SNPs within or near IFNL4 such as rs12979860 and rs8099917. Intrahepatic expression levels of IFN-stimulated genes (ISGs) affect the responsiveness to IFNα and are also associated with IFNL4 genotype...
December 30, 2016: Journal of Medical Virology
https://www.readbyqxmd.com/read/28035359/isg15-inhibits-cancer-cell-growth-and-promotes-apoptosis
#13
Mei-Juan Zhou, Fang-Zhi Chen, Han-Chun Chen, Xin-Xing Wan, Xi Zhou, Qian Fang, Dian-Zheng Zhang
Cervical cancer is one of the most common causes of cancer-related mortality in women in developing countries. Interferon (IFN)-α has been widely used in the treatment of various types of cancer, including cervical cancer, and IFN-stimulated gene 15 (ISG15), an ubiquitin-like protein, is upregulated by IFN-α treatment. The anti-virus and antitumor effects of ISG15 have been reported; however, its mechanism of action have not yet been fully elucidated. In this study, HeLa cells were used as a model system to investigate the roles of ISG15 in IFN-α-mediated cancer cell growth inhibition and induction of apoptosis...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28018302/proteomic-analysis-of-differential-expression-of-cellular-proteins-in-response-to-avian-h9n2-virus-infection-of-a549-cells
#14
Guanliu Yu, Wei Liang, Jiyuan Liu, Dan Meng, Liangmeng Wei, Tongjie Chai, Yumei Cai
In this study, differentially expressed proteins in A549 cells (human lung adenocarcinoma epithelial cell line) infected with H9N2 avian influenza virus (AIV) were investigated by two-dimensional electrophoresis (2-DE). Sixteen different spots between the groups (ratio > 2, p < 0.05) were identified with mass spectrometry identification. Proteins located in the downstream of the NF-κB and IFN transcription factor pathways were identified, e.g., ISG15. Actin and keratin were also identified, suggesting that the cytoskeleton may plays an important role in the AIV infection of mammalian cells...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28012987/characterization-of-non-lethal-west-nile-virus-wnv-infection-in-horses-subclinical-pathology-and-innate-immune-response
#15
Helle Bielefeldt-Ohmann, Angela Bosco-Lauth, Airn-Elizabeth Hartwig, M Jasim Uddin, Jean Barcelon, Willy W Suen, Wenqi Wang, Roy A Hall, Richard A Bowen
Most natural West Nile virus (WNV) infections in humans and horses are subclinical or sub-lethal and non-encephalitic. Yet, the main focus of WNV research remains on the pathogenesis of encephalitic disease, mainly conducted in mouse models. We characterized host responses during subclinical WNV infection in horses and compared outcomes with those obtained in a novel rabbit model of subclinical WNV infection (Suen et al. 2015. Pathogens, 4: 529). Experimental infection of 10 horses with the newly emerging WNV-strain, WNVNSW2011, did not result in neurological disease in any animal but transcriptional upregulation of both type I and II interferon (IFN) was seen in peripheral blood leukocytes prior to or at the time of viremia...
December 21, 2016: Microbial Pathogenesis
https://www.readbyqxmd.com/read/27988795/a-novel-anti-viral-role-for-stat3-in-ifn-%C3%AE-signalling-responses
#16
Rebecca Mahony, Siobhán Gargan, Kim L Roberts, Nollaig Bourke, Sinead E Keating, Andrew G Bowie, Cliona O'Farrelly, Nigel J Stevenson
The cytokine, Interferon (IFN)-α, induces a wide spectrum of anti-viral mediators, via the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. STAT1 and STAT2 are well characterised to upregulate IFN-stimulated gene (ISG) expression; but even though STAT3 is also activated by IFN-α, its role in anti-viral ISG induction is unclear. Several viruses, including Hepatitis C and Mumps, reduce cellular STAT3 protein levels, via the promotion of ubiquitin-mediated proteasomal degradation...
December 17, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27980214/the-isg15-specific-protease-usp18-regulates-stability-of-pten
#17
Lisa Maria Mustachio, Masanori Kawakami, Yun Lu, Jaime Rodriguez-Canales, Barbara Mino, Carmen Behrens, Ignacio Wistuba, Neus Bota-Rabassedas, Jun Yu, J Jack Lee, Jason Roszik, Lin Zheng, Xi Liu, Sarah J Freemantle, Ethan Dmitrovsky
The ubiquitin-like modifier interferon-stimulated gene 15 (ISG15) is implicated in both oncogenic and tumor suppressive programs. Yet, few ISGylation substrates are known and functionally validated in cancer biology. We previously found specific oncoproteins were substrates of ISGylation and were stabilized by the ISG15-specific deubiquitinase (DUB) ubiquitin specific peptidase 18 (USP18). Using reverse-phase protein arrays (RPPAs), this study reports that engineered loss of the DUB USP18 destabilized the tumor suppressor protein phosphatase and tensin homologue (PTEN) in both murine and human lung cancer cell lines...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27895186/correction-for-eduardo-correia-et-al-isg15-is-counteracted-by-vaccinia-virus-e3-protein-and-controls-the-proinflammatory-response-against-viral-infection
#18
Benedito Eduardo-Correia, Carles Martínez-Romero, Adolfo García-Sastre, Susana Guerra
No abstract text is available yet for this article.
December 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27888627/identification-of-differentially-expressed-genes-in-the-development-of-osteosarcoma-using-rna-seq
#19
Yihao Yang, Ya Zhang, Xin Qu, Junfeng Xia, Dongqi Li, Xiaojuan Li, Yu Wang, Zewei He, Su Li, Yonghong Zhou, Lin Xie, Zuozhang Yang
OBJECTIVE: Osteosarcoma (OS) is a malignant bone tumor with high morbidity in young adults and adolescents. This study aimed to discover potential early diagnosis biomarkers in OS. RESULTS: In total, 111 differentially expressed genes (DEGs) were identified in primary OS compared with normal controls and 235 DEGs were identified in metastatic OS compared with primary OS. AURKB and PPP2R2B were the significantly up-regulated and down-regulated hub proteins, respectively, in the PPI protein-protein network (PPI) network of primary OS...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27887993/isg15-in-sickness-and-in-health
#20
REVIEW
Mark Hermann, Dusan Bogunovic
ISG15 is a type I interferon (IFN)-inducible gene encoding a protein with pleiotropic functions, acting both as a soluble molecule and as a protein modifier. Surprisingly, and despite the antiviral functions of ISG15 described in mice, humans born with inactivating mutations of ISG15 do not present with any overt viral phenotype, but are highly susceptible to environmental mycobacteria and have autoinflammatory disease presentations. In vitro, ISG15 deficiency also leads to persistently high levels of type I IFN-stimulated gene expression and to increased resistance to all viruses tested to date...
November 22, 2016: Trends in Immunology
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