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https://www.readbyqxmd.com/read/29037975/modular-cell-based-platform-for-high-throughput-identification-of-compounds-that-inhibit-a-viral-interferon-antagonist-of-choice
#1
Andri Vasou, Christina Paulus, Janina Narloch, Zoe O Gage, Marie-Anne Rameix-Welti, Jean-François Eléouët, Michael Nevels, Richard E Randall, Catherine S Adamson
Viral interferon (IFN) antagonists are a diverse class of viral proteins that counteract the host IFN response, which is important for controlling viral infections. Viral IFN antagonists are often multifunctional proteins that perform vital roles in virus replication beyond IFN antagonism. The critical importance of viral IFN antagonists is highlighted by the fact that almost all viruses encode one of these proteins. Inhibition of viral IFN antagonists has the potential to exert pleiotropic antiviral effects and thus this important protein class represents a diverse plethora of novel therapeutic targets...
October 13, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29024766/protective-effect-of-an-alpha-7-nicotinic-acetylcholine-receptor-agonist-against-enterovirus-71-infection-in-neuronal-cells
#2
FengXia Song, LinQin Zhao, RuNan Zhu, QinWei Song, Jie Deng, Run Tian, Fang Wang, Yuan Qian
Enterovirus 71, as one of the dominant pathogens associated with severe hand, foot, and mouth disease, has been well reported to trigger severe neurological symptoms among young children over the last decade, particularly among children in the Asia-Pacific region. To date, no effective antiviral agent has been developed for the treatment of severe enterovirus 71 infection. PNU-282987, a selective alpha 7 nicotinic acetylcholine receptor (α7nAChR) agonist, has been reported to have a neuroprotective effect by participating in inflammatory regulation in previous studies...
October 9, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28988797/altered-expression-of-interferon-stimulated-genes-is-strongly-associated-with-therapeutic-outcomes-in-hepatitis-b-virus-infection
#3
Meifang Han, Yong Li, Wenyu Wu, Yuanya Zhang, Weiming Yan, Xiaoping Luo, Qin Ning
Our previous OSST study shows that switching to pegylated interferon (Peg-IFN)-α2a results in higher rates of response hepatitis B e antigen (HBeAg) seroconversion and hepatitis B surface antigen (HBsAg) loss at the end of treatment, compared with nucleot(s)ide analogues (NAs) monotherapy in long term NA-treated chronic hepatitis B (CHB) patients. In order to characterize the correlation between Peg-IFN-α antiviral effect and IFN-inducing signaling in CHB patients who switched to Peg-IFN from long time entecavir (ETV) treatment, we investigated the dynamic expression of interferon-stimulated genes (ISGs), including STAT1, MX, and a negative regulatory factor, suppressor of cytokine signaling 3(SOCS3), which negatively regulate IFN JAK-STAT signaling pathway by interacting with STAT1 and STAT2, in peripheral blood and paired liver samples, obtained from 54 CHB patients enrolled in a clinical trial, OSST study...
October 6, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28978648/structural-analysis-of-the-stat1-stat2-heterodimer-revealed-the-mechanism-of-sendai-virus-c-protein-mediated-blockade-of-type-1-interferon-signaling
#4
Kosuke Oda, Takashi Oda, Yasuyuki Matoba, Mamoru Sato, Takashi Irie, Takemasa Sakaguchi
Sendai virus (SeV), which causes respiratory diseases in rodents, possesses the C protein that blocks the signal transduction of interferon (IFN), thereby escaping from host innate immunity. We previously demonstrated by using protein crystallography that two molecules of Y3 (C-terminal half of C protein) can bind to the homodimer of the N-terminal domain of STAT1 (STAT1ND), elucidating the mechanism of inhibition of IFN-γ signal transduction. SeV C protein also blocks the signal transduction of IFN-α/β by inhibiting the phosphorylation of STAT1 and STAT2, although the mechanism for the inhibition is unclear...
October 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28973998/protein-inhibitor-of-activated-stat2-restricts-hcv-replication-by-modulating-viral-proteins-degradation
#5
Jing Guo, Dan Chen, Xiaoxiao Gao, Xue Hu, Yuan Zhou, Chunchen Wu, Yun Wang, Jizheng Chen, Rongjuan Pei, Xinwen Chen
Hepatitis C virus (HCV) replication in cells is controlled by many host factors. In this report, we found that protein inhibitor of activated STAT2 (PIAS2), which is a small ubiquitin-like modifier (SUMO) E3 ligase, restricted HCV replication. During infection, HCV core, NS3 and NS5A protein expression, as well as the viral assembly and budding efficiency were enhanced when endogenous PIAS2 was knocked down, whereas exogenous PIAS2 expression decreased HCV core, NS3, and NS5A protein expression and the viral assembly and budding efficiency...
September 30, 2017: Viruses
https://www.readbyqxmd.com/read/28912762/comparative-study-of-transcriptome-profiles-of-mouse-livers-and-skins-infected-by-fork-tailed-or-non-fork-tailed-schistosoma-japonicum
#6
Yan Yang, Jun-Jun He, Shuang Hu, Hua Chang, Xun Xiang, Jian-Fa Yang, Feng-Cai Zou
Schistosoma japonicum (S. japonicum) is a worldwide spread pathogen which penetrates host skin and then induces several diseases in infected host, such as fibrosis, formation of granulomas, hepatocirrhosis, and hepatomegaly. In present study, for the first time, transcriptomic profiles of mouse livers and skins infected by fork-tailed S. japonicum cercaria or non-fork-tailed S. japonicum cercaria were analyzed by using RNA-seq. The present findings demonstrated that transcriptomic landscapes of livers and skins infected by fork-tailed S...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28871140/increased-incidence-of-cytomegalovirus-coinfection-in-hcv-infected-patients-with-late-liver-fibrosis-is-associated-with-dysregulation-of-jak-stat-pathway
#7
Marwa K Ibrahim, Ahmed Khedr, Noha G Bader El Din, Ahmed Khairy, Mostafa K El Awady
Herein, we examined the association between cytomegalovirus (CMV) coinfection and the progression of liver fibrosis in hepatitis C virus (HCV) infection, and investigated the effect of CMV coinfection on JAK-STAT pathway. CMV DNAemia was detected by PCR in DNA from controls (n = 120), and HCV patients with early (F0-F1, n = 131) and late (F2-F4, n = 179) liver fibrosis. By quantitative real time PCR (qRT-PCR), we examined the profile of 8 JAK-STAT transcripts in PBMCs RNA from 90 HCV patients (39 CMV positive and 51 CMV negative), 4 CMV mono-infected patients, and 15 controls...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28870857/molecular-characterization-and-expression-analysis-of-interferon-gamma-in-black-seabream-acanthopagrus-schlegelii
#8
Yangxi Xiang, Wei Liu, Peng Jia, Yunlong Li, Yilin Jin, Limin Chen, Jing Zhang, Kuntong Jia, Meisheng Yi
Interferon gamma (IFN-γ) is a major component in immunological signaling and plays a key role in resisting viral infection. In this study, we identified and characterized an IFN-γ gene (AsIFN-γ) in the marine fish black seabream (Acanthopagrus schlegelii). We cloned AsIFN-γ genomic sequence, which comprises four exons, three introns and an upstream promoter including several conserved regulatory elements. The complete cDNA of AsIFN-γ was 816 bp in length and encoded a putative 194 amino acids (aa) protein with a 22 aa signal peptide, six α-helices and one nuclear localization signal (NLS)...
September 7, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28866137/aedes-aegypti-saliva-enhances-chikungunya-virus-replication-in-human-skin-fibroblasts-via-inhibition-of-the-type-i-interferon-signaling-pathway
#9
Sineewanlaya Wichit, Fodé Diop, Rodolphe Hamel, Loïc Talignani, Pauline Ferraris, Sylvie Cornelie, Florian Liegeois, Frédéric Thomas, Hans Yssel, Dorothée Missé
Chikungunya virus (CHIKV) transmission occurs through the bite of an infected Aedes mosquito which injects virus-containing saliva into the skin of the human host during blood feeding. In the present study, we have determined the effect of Aedes aegypti saliva on CHIKV replication in human skin fibroblasts, a major cell type for viral entry, which mimics the events that occur during natural transmission. A significant increase in the expression of viral transcripts and infectious viral particles was observed in fibroblasts infected with CHIKV in the presence of saliva, as compared with those infected with virus alone...
September 1, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28865344/heartland-virus-infection-in-hamsters-deficient-in-type-i-interferon-signaling-protracted-disease-course-ameliorated-by-favipiravir
#10
Jonna B Westover, Johanna D Rigas, Arnaud J Van Wettere, Rong Li, Brady T Hickerson, Kie-Hoon Jung, Jinxin Miao, Erin S Reynolds, Bettina L Conrad, Skot Nielson, Yousuke Furuta, Saravanan Thangamani, Zhongde Wang, Brian B Gowen
Heartland virus (HRTV) is an emerging tick-borne virus (Bunyaviridae, Phlebovirus) that has caused sporadic cases of human disease in several central and mid-eastern states of America. Animal models of HRTV disease are needed to gain insights into viral pathogenesis and advancing antiviral drug development. Presence of clinical disease following HRTV challenge in hamsters deficient in STAT2 function underscores the important role played by type I interferon-induced antiviral responses. However, the recovery of most of the infected animals suggests that other mechanisms to control infection and limit disease offer substantial protection...
November 2017: Virology
https://www.readbyqxmd.com/read/28835499/nipah-and-hendra-virus-nucleoproteins-inhibit-nuclear-accumulation-of-signal-transducer-and-activator-of-transcription-1-stat1-and-stat2-by-interfering-with-their-complex-formation
#11
Akihiro Sugai, Hiroki Sato, Ikuyo Takayama, Misako Yoneda, Chieko Kai
Henipaviruses, such as Nipah (NiV) and Hendra (HeV) viruses, are highly pathogenic zoonotic agents within the Paramyxoviridae family. The phosphoprotein (P) gene products of the paramyxoviruses have been well characterized for their interferon (IFN) antagonist activity and their contribution to viral pathogenicity. In this study, we demonstrated that the nucleoprotein (N) of henipaviruses also prevents the host IFN signaling response. Reporter assays demonstrated that the NiV and HeV N proteins (NiV-N and HeV-N, respectively) dose-dependently suppressed both type I and type II IFN responses and that the inhibitory effect was mediated by their core domains...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28827743/mir-125a-mir-139-and-mir-324-contribute-to-urocortin-protection-against-myocardial-ischemia-reperfusion-injury
#12
Ignacio Díaz, Eva Calderón-Sánchez, Raquel Del Toro, Javier Ávila-Médina, Eva Sánchez de Rojas-de Pedro, Alejandro Domínguez-Rodríguez, Juan Antonio Rosado, Abdelkrim Hmadcha, Antonio Ordóñez, Tarik Smani
Urocortin 1 and 2 (Ucn-1 and Ucn-2) have established protective actions against myocardial ischemia-reperfusion (I/R) injuries. However, little is known about their role in posttranscriptional regulation in the process of cardioprotection. Herein, we investigated whether microRNAs play a role in urocortin-induced cardioprotection. Administration of Ucn-1 and Ucn-2 at the beginning of reperfusion significantly restored cardiac function, as evidenced ex vivo in Langendorff-perfused rat hearts and in vivo in rat subjected to I/R...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818566/a-synthetic-human-cytomegalovirus-pp65-ie1-fusion-antigen-efficiently-induces-and-expands-virus-specific-t-cells
#13
Ellen K Link, Christine Brandmüller, Yasemin Suezer, Stefanie Ameres, Asisa Volz, Andreas Moosmann, Gerd Sutter, Michael H Lehmann
Infection with human cytomegalovirus (HCMV) can cause severe complications in newborns and immunocompromised patients, and a prophylactic or therapeutic vaccine against HCMV is not available. Here, we generated a HCMV vaccine candidate fulfilling the regulatory requirements for GMP-compliant production and clinical testing. A novel synthetic fusion gene consisting of the coding sequences of HCMV pp65 and IE1 having a deleted nuclear localization sequence and STAT2 binding domain was introduced into the genome of the attenuated vaccinia virus strain MVA...
August 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28808111/interferon-tau-promotes-cell-survival-and-inhibits-specific-luteolytic-genes-in-bovine-corpus-luteum
#14
Raghavendra Basavaraja, Emilia Przygrodzka, Bartosz Pawlinski, Zdzislaw Gajewski, Monika Marzena Kaczmarek, Rina Meidan
Interferon-tau (IFNT), a maternal recognition of pregnancy signals in domestic ruminants, suppress the release of luteolytic pulses of uterine prostaglandin F2a (PGF2a), thus extending the corpus luteum (CL) life span. We hypothesized that IFNT also exerts anti-luteolytic actions in bovine CL. To examine the direct effects of IFNT on bovine CL, luteal slices and enriched luteal endothelial cells (LECs) were utilized. We found that recombinant ovine IFNT (roIFNT) markedly elevates interferon-associated genes (STAT1, STAT2, and IRF9) and interferon-stimulated genes (ISGs: MX2, ISG15, & OAS1Y) in both models...
August 14, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28765967/influenza-virus-non%C3%A2-structural-protein-1-inhibits-the-production-of-interferon-%C3%AE-of-alveolar-epithelial-cells-upon-the-infection-of-influenza-a-h1n1
#15
Hao Jiang, Si-Mei Shen, Jie Yin, Peng-Peng Zhang, Yi Shi
Influenza A affects a large population worldwide. Influenza virus evades immune responses via various mechanisms, including through the modification of the immune microenvironment. Influenza virus non‑structural protein 1 (NS1) encoded by the virus genome inhibits type I interferon (IFN) signaling pathways, which is essential for viral clearance. However, the precise mechanisms of NS1‑mediated immune suppression remain poorly understood. The results of the present study demonstrated that mice infected with NS1‑expressing influenza A H1N1 virus had lower expression levels of IFNβ in the lung...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28747540/chronicling-the-discovery-of-interferon-tau
#16
REVIEW
Fuller W Bazer, William W Thatcher
It has been 38 years since a protein, now known as interferon tau (IFNT), was discovered in ovine conceptus-conditioned culture medium. After 1979, purification and testing of native IFNT revealed its unique antiluteolyic activity to prevent the regression of corpora lutea on ovaries of nonpregnant ewes. Antiviral, antiproliferative and immunomodulatory properties of native and recombinant IFNT were demonstrated later. In addition, progesterone and IFNT were found to act cooperatively to silence expression of classical interferon stimulated genes in a cell-specific manner in ovine uterine luminal and superficial glandular epithelia...
November 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28714361/rna-editing-is-induced-by-type-i-interferon-in-esophageal-squamous-cell-carcinoma
#17
Jinyao Zhang, Zhaoli Chen, Zefang Tang, Jianbing Huang, Xueda Hu, Jie He
In recent years, abnormal RNA editing has been shown to play an important role in the development of esophageal squamous cell carcinoma, as such abnormal editing is catalyzed by ADAR (adenosine deaminases acting on RNA). However, the regulatory mechanism of ADAR1 in esophageal squamous cell carcinomas remains largely unknown. In this study, we investigated ADAR1 expression and its association with RNA editing in esophageal squamous cell carcinomas. RNA sequencing applied to esophageal squamous cell carcinoma clinical samples showed that ADAR1 expression was correlated with the expression of STAT1, STAT2, and IRF9...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28711499/inhibition-of-il-6-stat3-signaling-in-human-cancer-cells-using-evista
#18
Wei Shi, Dan Yan, Chongqiang Zhao, Miaomiao Xiao, Yina Wang, Haiyan Ma, Tianshu Liu, Hua Qin, Cuntai Zhang, Chenglong Li, Jiayuh Lin, Sheng Li, Jiagao Lv, Li Lin
Persistent activation of IL-6/STAT3 signaling pathway has been frequently detected in human cancer including breast cancer, colon cancer and multiple myeloma. IL-6/STAT3 can be a promising target for cancer prevent and treatment. However, few STAT3 inhibitors with high efficiency, specificity and safety is available for present clinical cancer therapy. Evista (Raloxifene·HCl) is known as selective estrogen receptor modulator which has been used for the prevention and treatment of osteoporosis and was approved for reducing the risk of invasive breast cancer...
September 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28707474/native-hydrophobic-binding-interactions-at-the-transition-state-for-association-between-the-taz1-domain-of-cbp-and-the-disordered-tad-stat2-are-not-a-requirement
#19
Ida Lindström, Jakob Dogan
A significant fraction of the eukaryotic proteome consists of proteins that are either partially or completely disordered under native-like conditions. Intrinsically disordered proteins (IDPs) are common in protein-protein interactions and are involved in numerous cellular processes. Although many proteins have been identified as disordered, much less is known about the binding mechanisms of the coupled binding and folding reactions involving IDPs. Here we have analyzed the rate-limiting transition state for binding between the TAZ1 domain of CREB binding protein and the intrinsically disordered transactivation domain of STAT2 (TAD-STAT2) by site-directed mutagenesis and kinetic experiments (Φ-value analysis) and found that the native protein-protein binding interface is not formed at the transition state for binding...
August 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28684637/interferon-stimulated-genes-are-transcriptionally-repressed-by-pr-in-breast-cancer
#20
Katherine R Walter, Merit L Goodman, Hari Singhal, Jade A Hall, Tianbao Li, Sean M Holloran, Gloria M Trinca, Katelin A Gibson, Victor X Jin, Geoffrey L Greene, Christy R Hagan
The progesterone receptor (PR) regulates transcriptional programs that drive proliferation, survival, and stem cell phenotypes. Although the role of native progesterone in the development of breast cancer remains controversial, PR clearly alters the transcriptome in breast tumors. This study identifies a class of genes, Interferon (IFN)-stimulated genes (ISGs), potently downregulated by ligand-activated PR which have not been previously shown to be regulated by PR. Progestin-dependent transcriptional repression of ISGs was observed in breast cancer cell line models and human breast tumors...
October 2017: Molecular Cancer Research: MCR
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