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Interferons and viral infections

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https://www.readbyqxmd.com/read/28545127/improvement-of-alt-decay-kinetics-by-all-oral-hcv-treatment-role-of-ns5a-inhibitors-and-differences-with-ifn-based-regimens
#1
Valeria Cento, Thi Huyen Tram Nguyen, Domenico Di Carlo, Elisa Biliotti, Laura Gianserra, Ilaria Lenci, Daniele Di Paolo, Vincenza Calvaruso, Elisabetta Teti, Maddalena Cerrone, Dante Romagnoli, Michela Melis, Elena Danieli, Barbara Menzaghi, Ennio Polilli, Massimo Siciliano, Laura Ambra Nicolini, Antonio Di Biagio, Carlo Federico Magni, Matteo Bolis, Francesco Paolo Antonucci, Velia Chiara Di Maio, Roberta Alfieri, Loredana Sarmati, Paolo Casalino, Sergio Bernardini, Valeria Micheli, Giuliano Rizzardini, Giustino Parruti, Tiziana Quirino, Massimo Puoti, Sergio Babudieri, Antonella D'Arminio Monforte, Massimo Andreoni, Antonio Craxì, Mario Angelico, Caterina Pasquazzi, Gloria Taliani, Jeremie Guedj, Carlo Federico Perno, Francesca Ceccherini-Silberstein
BACKGROUND: Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR. STUDY DESIGN: Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR...
2017: PloS One
https://www.readbyqxmd.com/read/28543875/unconjugated-interferon-stimulated-gene-15-specifically-interacts-with-the-hepatitis-c-virus-ns5a-protein-via-domain-i
#2
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
#3
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 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542326/the-murine-cytomegalovirus-m35-protein-antagonizes-type-i-ifn-induction-downstream-of-pattern-recognition-receptors-by-targeting-nf-%C3%AE%C2%BAb-mediated-transcription
#4
Baca Chan, Vladimir Gonçalves Magalhães, Niels A W Lemmermann, Vanda Juranić Lisnić, Markus Stempel, Kendra A Bussey, Elisa Reimer, Jürgen Podlech, Stefan Lienenklaus, Matthias J Reddehase, Stipan Jonjić, Melanie M Brinkmann
The type I interferon (IFN) response is imperative for the establishment of the early antiviral immune response. Here we report the identification of the first type I IFN antagonist encoded by murine cytomegalovirus (MCMV) that shuts down signaling following pattern recognition receptor (PRR) sensing. Screening of an MCMV open reading frame (ORF) library identified M35 as a novel and strong negative modulator of IFNβ promoter induction following activation of both RNA and DNA cytoplasmic PRR. Additionally, M35 inhibits the proinflammatory cytokine response downstream of Toll-like receptors (TLR)...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28539639/the-absence-of-interferon-%C3%AE-promotor-stimulator-1-ips-1-predisposes-to-bronchiolitis-and-asthma-like-pathology-in-response-to-pneumoviral-infection-in-mice
#5
Jennifer Simpson, Jason P Lynch, Zhixuan Loh, Vivian Zhang, Rhiannon B Werder, Kirsten Spann, Simon Phipps
Respiratory syncytial virus (RSV)-bronchiolitis is a major cause of infant morbidity and mortality and a risk factor for subsequent asthma. We showed previously that toll-like receptor (TLR)7 in plasmacytoid dendritic cells (pDCs) is critical for protection against bronchiolitis and asthma in mice infected with pneumonia virus of mice (PVM), the mouse homolog of RSV. This lack of redundancy was unexpected as interferon-β promotor stimulator-1 (IPS-1) signalling, downstream of RIG-I-like receptor (RLR) and not TLR7 activation, contributes to host defence in hRSV-inoculated adult mice...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539444/improved-prefusion-stability-optimized-codon-usage-and-augmented-virion-packaging-enhance-the-immunogenicity-of-respiratory-syncytial-virus-rsv-fusion-protein-in-a-vectored-vaccine-candidate
#6
Bo Liang, Joan O Ngwuta, Sonja Surman, Barbora Kabatova, Xiang Liu, Matthias Lingemann, Xueqiao Liu, Lijuan Yang, Richard Herbert, Joanna Swerczek, Man Chen, Syed M Moin, Azad Kumar, Jason S McLellan, Peter D Kwong, Barney S Graham, Peter L Collins, Shirin Munir
Respiratory syncytial virus (RSV) is the most important viral agent of severe pediatric respiratory tract disease worldwide, but lacks a licensed vaccine or suitable antiviral drug. A live-attenuated chimeric bovine/human parainfluenza virus type-3 (rB/HPIV3) was developed previously as a vector expressing RSV fusion (F) protein to confer bivalent protection against RSV and HPIV3. In a previous clinical trial in virus-naïve children, rB/HPIV3 was well-tolerated but the immunogenicity of wildtype RSV F was unsatisfactory...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539069/real-world-challenges-for-hepatitis-c-virus-medications-a-critical-overview
#7
Imran Shahid, Waleed Hassan AlMalki, Sajida Hassan, Muhammad Hassan Hafeez
From 2010, the landscape of hepatitis C therapeutics has been changed rapidly, and today we are standing at a cusp of a pharmacological revolution where highly effective and interferon (IFN)-free direct acting antivirals (DAAs) are already on the market. Such treatment paradigms attain 90-95% sustained virologic response (SVR; undetectable viral load at week 12 or 24 at the end of therapy) rates in treated individuals compared to 50-70% with treatment completion of dual-therapy-pegylated interferon (PEG-IFN) and ribavirin (RBV)...
May 25, 2017: Critical Reviews in Microbiology
https://www.readbyqxmd.com/read/28537249/airway-t-cells-protect-against-rsv-infection-in-the-absence-of-antibody
#8
E Kinnear, L Lambert, J U McDonald, H M Cheeseman, L J Caproni, J S Tregoning
Tissue resident memory T (Trm) cells act as sentinels and early responders to infection. Respiratory syncytial virus (RSV)-specific Trm cells have been detected in the lungs after human RSV infection, but whether they have a protective role is unknown. To dissect the protective function of Trm cells, BALB/c mice were infected with RSV; infected mice developed antigen-specific CD8(+) Trm cells (CD103(+)/CD69(+)) in the lungs and airways. Intranasally transferring cells from the airways of previously infected animals to naïve animals reduced weight loss on infection in the recipient mice...
May 24, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28536674/anti-idiotypic-antibodies-specific-to-prm-monoantibody-prevent-antibody-dependent-enhancement-of-dengue-virus-infection
#9
Miao Wang, Fan Yang, Dana Huang, Yalan Huang, Xiaomin Zhang, Chao Wang, Shaohua Zhang, Renli Zhang
Dengue virus (DENV) co-circulates as four serotypes (DENV1-4). Primary infection only leads to self-limited dengue fever. But secondary infection with another serotype carries a higher risk of increased disease severity, causing life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Serotype cross-reactive antibodies facilitate DENV infection in Fc-receptor-bearing cells by promoting virus entry via Fcγ receptors (FcγR), a process known as antibody dependent enhancement (ADE). Most studies suggested that enhancing antibodies were mainly specific to the structural premembrane protein (prM) of DENV...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28536390/showing-the-way-oncolytic-adenoviruses-as-chaperones-of-immunostimulatory-adjuncts
#10
REVIEW
Jing Li Huang, Christopher J LaRocca, Masato Yamamoto
Oncolytic adenoviruses (OAds) are increasingly recognized as vectors for immunotherapy in the treatment of various solid tumors. The myriads of advantages of using adenovirus include targeted specificity upon infection and selective replication, which lead to localized viral burst, exponential spread of OAds, and antitumor effect. OAds can also induce a strong immune reaction due to the massive release of tumor antigens upon cytolysis and the presence of viral antigens. This review will highlight recent advances in adenoviral vectors expressing immunostimulatory effectors, such as GM-CSF (granulocyte macrophage colony-stimulating factor), interferon-α, interleukin-12, and CD40L...
September 19, 2016: Biomedicines
https://www.readbyqxmd.com/read/28531865/glutamine-antagonist-mediated-immune-suppression-decreases-pathology-but-delays-virus-clearance-in-mice-during-nonfatal-alphavirus-encephalomyelitis
#11
Victoria K Baxter, Rebecca Glowinski, Alicia M Braxton, Michelle C Potter, Barbara S Slusher, Diane E Griffin
Infection of weanling C57BL/6 mice with the TE strain of Sindbis virus (SINV) causes nonfatal encephalomyelitis associated with hippocampal-based memory impairment that is partially prevented by treatment with 6-diazo-5-oxo-l-norleucine (DON), a glutamine antagonist (Potter et al., J Neurovirol 21:159, 2015). To determine the mechanism(s) of protection, lymph node and central nervous system (CNS) tissues from SINV-infected mice treated daily for 1 week with low (0.3mg/kg) or high (0.6mg/kg) dose DON were examined...
May 19, 2017: Virology
https://www.readbyqxmd.com/read/28530712/the-microrna-mir-31-inhibits-cd8-t-cell-function-in-chronic-viral-infection
#12
Howell F Moffett, Adam N R Cartwright, Hye-Jung Kim, Jernej Godec, Jason Pyrdol, Tarmo Äijö, Gustavo J Martinez, Anjana Rao, Jun Lu, Todd R Golub, Harvey Cantor, Arlene H Sharpe, Carl D Novina, Kai W Wucherpfennig
During infection, antigen-specific T cells undergo tightly regulated developmental transitions controlled by transcriptional and post-transcriptional regulation of gene expression. We found that the microRNA miR-31 was strongly induced by activation of the T cell antigen receptor (TCR) in a pathway involving calcium and activation of the transcription factor NFAT. During chronic infection with lymphocytic choriomeningitis virus (LCMV) clone 13, miR-31-deficent mice recovered from clinical disease, while wild-type mice continued to show signs of disease...
May 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28530508/influence-of-transmitted-virus-on-the-host-s-immune-response-a-case-study
#13
Shahzma Merani, Michaela Lucas, Pooja Deshpande, Katja Pfafferott, Abha Chopra, Don Cooper, Shay Leary, Fabio Luciani, Silvana Gaudieri
Host hepatitis C virus (HCV)-specific T cell responses and the ability of the virus to escape this response are important correlates of infection outcome. Understanding this host-viral interplay has been difficult given the often asymptomatic nature of acute HCV infection. We studied a recent transmission case to determine whether adapted viral strains can be transmitted and influence the recipient's anti-HCV T cell response. The diversity of viral populations was examined using next-generation sequencing, and HCV-specific T cell interferon (IFN)-γ responses were assessed using a peptide panel representing the autologous viruses...
May 22, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28529959/getting-inside-type-i-ifns-type-i-ifns-in-intracellular-bacterial-infections
#14
REVIEW
Deann T Snyder, Jodi F Hedges, Mark A Jutila
Type I interferons represent a unique and complex group of cytokines, serving many purposes during innate and adaptive immunity. Discovered in the context of viral infections, type I IFNs are now known to have myriad effects in infectious and autoimmune disease settings. Type I IFN signaling during bacterial infections is dependent on many factors including whether the infecting bacterium is intracellular or extracellular, as different signaling pathways are activated. As such, the repercussions of type I IFN induction can positively or negatively impact the disease outcome...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28527896/molecular-characterization-and-expression-analyses-of-the-solea-senegalensis-interferon-stimulated-gene-15-isg15-following-nnv-infections
#15
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/28523924/comparison-of-transcriptional-profiles-of-interferons-cxcl10-and-rig-1-in-influenza-infected-a549-cells-stimulated-with-exogenous-interferons
#16
V Lachová, L Škorvanová, D Svetlíková, L Turianová, A Kostrábová, T Betáková
Type I and type III interferons (IFNs) are induced by viral infection. It was concluded that these IFN species are identical in regulation and biological functions. However, these two systems differ in the tissue expression of their receptors and their transcriptional regulation is fundamentally different as well as cellular signaling pathways that drive expression of each IFN. Here, we have investigated the transcriptional profile of endogenous IFNs after stimulation of cells with exogenous IFNs and subsequent infection of A549 cells with A/chicken/Germany/27 [H7N7] influenza virus...
2017: Acta Virologica
https://www.readbyqxmd.com/read/28523305/the-impact-of-liver-steatosis-on-early-and-sustained-treatment-response-in-chronic-hepatitis-c-patients
#17
Alice Elena Găman, Anca Marilena Ungureanu, Adriana Turculeanu, Dan IonuŢ Gheonea, Andrei Ioan Drocaş, George Mitroi, Maria DobriŢoiu, Maria Victoria Comănescu, Andreea Doriana Stănculescu, Ramona Cioboată, Claudiu Florin Jieanu, Paul Ioan Tomescu
Steatosis is a frequent feature of hepatitis C virus (HCV) infection. Steatosis may be an important cofactor in both accelerating fibrosis and increasing liver necroinflammatory activity in chronic hepatitis C. The main objective of this study was the evaluation of biological response rates, early viral response, sustained viral response in patients with chronic hepatitis C treated with Interferon-alpha (IFN-α), Pegylated (PEG)-IFN-α2a or -α2b plus Ribavirin and to relate it to the presence of hepatic steatosis...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28521677/molluscum-contagiosum-an-update
#18
Alexander Kc Leung, Benjamin Barankin, Kam Lun Hon
BACKGROUND: Molluscum contagiosum is a viral cutaneous infection in childhood that occurs worldwide. Physicians should familiarize themselves with this common condition. OBJECTIVE: To review in depth the epidemiology, pathophysiology, clinical manifestations, complications and, in particular, treatment of molluscum contagiosum. METHODS: A PubMed search was completed in Clinical Queries using the key term "molluscum contagiosum". Patents were searched using the key term "molluscum contagiosum" from www...
May 17, 2017: Recent Patents on Inflammation & Allergy Drug Discovery
https://www.readbyqxmd.com/read/28521640/antibody-mediated-immunotherapy-against-chronic-hepatitis-b-virus-infection
#19
Ying Gao, Tian-Ying Zhang, Quan Yuan, Ning-Shao Xia
The currently available drugs to treat hepatitis B virus (HBV) infection include interferons and nucleos(t)ide analogues, which can only induce disease remission and are inefficient for the functional cure of patients with chronic HBV infection (CHB). Since high titers of circulating hepatitis B surface antigen (HBsAg) may be essential to exhaust the host anti-HBV immune response and they cannot be significantly reduced by current drugs, new antiviral strategies aiming to suppress serum hepatitis B surface antigen (HBsAg) could help restore virus-specific immune responses and promote the eradication of the virus...
May 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28521211/hepatitis-c-virus-core-antigen-a-simplified-treatment-monitoring-tool-including-for-post-treatment-relapse
#20
François M J Lamoury, Angelica Soker, Danica Martinez, Behzad Hajarizadeh, Evan B Cunningham, Philip Cunningham, Philip Bruggmann, Graham R Foster, Olav Dalgard, Markus Backmund, Brian Conway, Geert Robaeys, Tracy Swan, Gavin Cloherty, Pip Marks, Jason Grebely, Gregory J Dore, Tanya L Applegate
BACKGROUND: Simple, affordable diagnostic tools are essential to facilitate global hepatitis C virus (HCV) elimination efforts. OBJECTIVES: This study evaluated the clinical performance of core antigen (HCVcAg) assay from plasma samples to monitor HCV treatment efficacy and HCV viral recurrence. STUDY DESIGN: Plasma samples from a study of response-guided pegylated-interferon/ribavirin therapy for people who inject drugs with chronic HCV genotype 2/3 infection were assessed for HCV RNA (AmpliPrep/COBAS Taqman assay, Roche) and HCVcAg (ARCHITECT HCV Ag, Abbott Diagnostics) during and after therapy...
May 11, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
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