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Interferons and viral infections

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https://www.readbyqxmd.com/read/27933565/kshv-strategies-for-host-dsdna-sensing-machinery
#1
REVIEW
Hang Gao, Yanyan Song, Chengrong Liu, Qiming Liang
The innate immune system utilizes pattern recognition receptors cyclic GMP-AMP synthase (cGAS) to sense cytosolic double-stranded (ds) DNA and initiate type 1 interferon signaling and autophagy pathway, which collaborate to limit pathogen infections as well as alarm the adaptive immune response. The genomes of herpesviruses are large dsDNA, which represent a major class of pathogen signatures recognized by cellular DNA sensor cGAS. However, to successfully establish the persistent infection, herpesviruses have evolved their viral genes to modulate different aspects of host immune signaling...
December 5, 2016: Virologica Sinica
https://www.readbyqxmd.com/read/27933051/short-interfering-rna-inhibits-rift-valley-fever-virus-replication-and-degradation-of-protein-kinase-r-in-human-cells
#2
Bonto Faburay, Juergen A Richt
Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing severe outbreaks in humans and livestock in sub-Saharan Africa and the Arabian Peninsula. Human infections are characterized by fever, sometimes leading to encephalitis, retinitis, hemorrhagic fever, and occasionally death. There are currently no fully licensed vaccines or effective therapies for human use. Gene silencing mediated by double-stranded short interfering RNA (siRNA) is a sequence-specific, highly conserved mechanism in eukaryotes, which serves as an antiviral defense mechanism...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27932023/molecular-cloning-and-expression-analysis-of-a-fish-specific-interferon-regulatory-factor-irf11-in-orange-spotted-grouper-epinephelus-coioides
#3
Wen Shu Huang, Mei Hua Zhu, Shan Chen, Zhi Xuan Wang, Ying Liang, Bei Huang, P Nie
Interferon regulatory factors (IRFs) are transcription mediators which play vital roles in multiple biological processes, such as antiviral defense, immune response, cell growth regulation and apoptosis. A fish specific IRF, termed IRF11, has been identified in previous study through searching fish genome databases. Herein, a transcript of IRF11, EcIRF11 was cloned from orange-spotted grouper, Epinephelus coioides. The EcIRF11 cDNA sequence has 1573 bp in length, encoding a putative protein of 261 amino acids, with a high degree of similarity found between EcIRF11 and its teleost counterparts...
December 5, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27931982/jak-inhibitor-tofacitinib-suppresses-interferon-alfa-production-by-plasmacytoid-dendritic-cells-and-inhibits-arthrogenic-and-antiviral-effects-of-interferon-alfa
#4
Patrick P C Boor, Petra E de Ruiter, Patrick S Asmawidjaja, Erik Lubberts, Luc J W van der Laan, Jaap Kwekkeboom
Tofacitinib is an oral Janus kinase inhibitor that is effective for the treatment of rheumatoid arthritis and shows encouraging therapeutic effects in several other autoimmune diseases. A prominent adverse effect of tofacitinib therapy is the increased risk of viral infections. Despite its advanced stage of clinical development, the modes of action that mediate the beneficial and adverse effects of tofacitinib in autoimmune diseases remain unclear. Interferon alfa (IFNα) produced by plasmacytoid dendritic cells (PDCs) is critically involved in the pathogenesis of many systemic autoimmune diseases and in immunity to viral infections...
November 20, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27929099/stat1-is-essential-for-the-inhibition-of-hepatitis-c-virus-replication-by-interferon-%C3%AE-but-not-by-interferon-%C3%AE
#5
Shota Yamauchi, Kenji Takeuchi, Kazuyasu Chihara, Chisato Honjoh, Yuji Kato, Hatsumi Yoshiki, Hak Hotta, Kiyonao Sada
Interferon-α (IFN-α) and IFN-λ are structurally distinct cytokines that bind to different receptors, but induce expression of similar sets of genes through Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathways. The difference between IFN-α and IFN-λ signaling remains poorly understood. Here, using the CRISPR/Cas9 system, we examine the role of STAT1 and STAT2 in the inhibition of hepatitis C virus (HCV) replication by IFN-α and IFN-λ. Treatment with IFN-α increases expression of IFN-stimulated genes (ISGs) such as double-stranded RNA-activated protein kinase (PKR) and decreases viral RNA and protein levels in HCV-infected Huh-7...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27927921/assessment-of-a-novel-automatic-real-time-pcr-assay-on-the-cobas4800-analyzer-as-a-screening-platform-for-hcv-genotyping-in-clinical-practice-comparison-with-massive-sequencing
#6
Leonardo Nieto-Aponte, Josep Quer, Alicia Ruiz-Ripa, David Tabernero, Carolina Gonzalez, Josep Gregori, Marta Vila, Miriam Asensio, Damir Garcia-Cehic, Gerardo Ruiz, Qian Chen, Laura Ordeig, Meritxell Llorens, Montserrat Saez, Juan I Esteban, Rafael Esteban, Maria Buti, Tomas Pumarola, Francisco Rodriguez-Frias
BACKGROUND: To optimize the effectiveness of interferon-free, direct-acting antiviral therapies for HCV, unequivocal identification of subtypes 1a/1b and genotypes 2 to 6 is required. METHODS: The performance of a new real-time HCV genotyping assay for use on the Cobas 4800 system (C4800) was compared with that of high-resolution HCV subtyping (HRCS). In total, 502 samples were included, 184 from chronic HCV patients (routine laboratory activity, April 2016), 5 stored samples with double HCV genotype infection to test the limitations of the method, and 313 from a screening protocol implemented in our hospital (May to August, 2016) based on the new method, to further determine its genotyping accuracy...
December 7, 2016: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/27926941/type-1-interferons-and-nk-cells-limit-murine-cytomegalovirus-escape-from-the-lymph-node-subcapsular-sinus
#7
Helen E Farrell, Kimberley Bruce, Clara Lawler, Rhonda D Cardin, Nicholas J Davis-Poynter, Philip G Stevenson
Cytomegaloviruses (CMVs) establish chronic, systemic infections. Peripheral infection spreads via lymph nodes, which are also a focus of host defence. Thus, this is a point at which systemic infection spread might be restricted. Subcapsular sinus macrophages (SSM) captured murine CMV (MCMV) from the afferent lymph and poorly supported its replication. Blocking the type I interferon (IFN-I) receptor (IFNAR) increased MCMV infection of SSM and of the fibroblastic reticular cells (FRC) lining the subcapsular sinus, and accelerated viral spread to the spleen...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27924822/il-21-dependent-expansion-of-memory-like-nk-cells-enhances-protective-immune-responses-against-mycobacterium-tuberculosis
#8
S Venkatasubramanian, S Cheekatla, P Paidipally, D Tripathi, E Welch, A R Tvinnereim, R Nurieva, R Vankayalapati
Natural killer (NK) cells are traditionally considered as innate cells, but recent studies suggest that NK cells can distinguish antigens, and that memory NK cells expand and protect against viral pathogens. Limited information is available about the mechanisms involved in memory-like NK cell expansion, and their role in bacterial infections and vaccine-induced protective immune responses. In the current study, using a mouse model of tuberculosis (TB) infection, we found that interferon-gamma producing CD3-NKp46+CD27+KLRG1+ memory-like NK cells develop during Bacille Calmette-Guérin vaccination, expand, and provide protection against challenge with Mycobacterium tuberculosis (M...
December 7, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27924780/activity-of-ergoferon-against-lethal-influenza-a-h3n2-virus-infection-in-mice
#9
Maria A Skarnovich, Alexandra G Emelyanova, Nataliia V Petrova, Alena A Borshcheva, Evgeniy A Gorbunov, Oleg Yu Mazurkov, Maksim O Skarnovich, Sergey A Tarasov, Larisa N Shishkina, Oleg I Epstein
BACKGROUND: The Influenza A virus accounts for serious annual viral upper respiratory tract infections. It is constantly able to modify its antigenic structure, thus evading host defence mechanisms. Moreover, currently available anti-influenza agents have a rather limited application, emphasising the further need for new effective treatments. One of them is Ergoferon, a drug, containing combined polyclonal antibodies - anti-interferon gamma, anti-CD4 receptor, and anti-histamine - in released-active form...
December 7, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/27923923/antiviral-innate-immune-response-interferes-with-the-formation-of-replication-associated-membrane-structures-induced-by-a-positive-strand-rna-virus
#10
Diede Oudshoorn, Barbara van der Hoeven, Ronald W A L Limpens, Corrine Beugeling, Eric J Snijder, Montserrat Bárcena, Marjolein Kikkert
: Infection with nidoviruses like corona- and arteriviruses induces a reticulovesicular network of interconnected endoplasmic reticulum (ER)-derived double-membrane vesicles (DMVs) and other membrane structures. This network is thought to accommodate the viral replication machinery and protect it from innate immune detection. We hypothesized that the innate immune response has tools to counteract the formation of these virus-induced replication organelles in order to inhibit virus replication...
December 6, 2016: MBio
https://www.readbyqxmd.com/read/27922126/viral-and-bacterial-co-infection-in-severe-pneumonia-triggers-innate-immune-responses-and-specifically-enhances-ip-10-a-translational-study
#11
Jonathan Hoffmann, Daniela Machado, Olivier Terrier, Stephane Pouzol, Mélina Messaoudi, Wilma Basualdo, Emilio E Espínola, Rosa M Guillen, Manuel Rosa-Calatrava, Valentina Picot, Thomas Bénet, Hubert Endtz, Graciela Russomando, Gláucia Paranhos-Baccalà
Mixed viral and bacterial infections are widely described in community-acquired pneumonia; however, the clinical implications of co-infection on the associated immunopathology remain poorly studied. In this study, microRNA, mRNA and cytokine/chemokine secretion profiling were investigated for human monocyte-derived macrophages infected in-vitro with Influenza virus A/H1N1 and/or Streptococcus pneumoniae. We observed that the in-vitro co-infection synergistically increased interferon-γ-induced protein-10 (CXCL10, IP-10) expression compared to the singly-infected cells conditions...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920482/hepatitis-c-virus-therapy-with-peg-interferon-and-ribavirin-in-myanmar-a-resource-constrained-country
#12
Naomi Khaing Than Hlaing, Debolina Banerjee, Robert Mitrani, Soe Htet Arker, Kyaw San Win, Nyan Lin Tun, Zaw Thant, Khin Maung Win, K Rajender Reddy
AIM: To investigate peg-interferon (peg-IFN) and ribavirin (RBV) therapy in Myanmar and to predict sustained virologic response (SVR). METHODS: This single-center, open-label, study was conducted in Myanmar between 2009 and 2014. A total of 288 patients infected with HCV genotypes 1, 2, 3 and 6 were treated with peg-IFN alpha-2a (180 μg/wk) or alpha-2b (50 to 100 μg as a weight-based dose) and RBV as a weight-based dose (15 mg/kg/d). Treatment duration was 48 wk for genotypes 1 and 6, 24 wk for genotype 2, and 24 or 48 wk for genotype 3 based on rapid virologic response (RVR)...
November 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27918527/induction-and-suppression-of-antiviral-rna-interference-by-influenza-a-virus-in-mammalian-cells
#13
Yang Li, Megha Basavappa, Jinfeng Lu, Shuwei Dong, D Alexander Cronkite, John T Prior, Hans-Christian Reinecker, Paul Hertzog, Yanhong Han, Wan-Xiang Li, Sihem Cheloufi, Fedor V Karginov, Shou-Wei Ding, Kate L Jeffrey
Influenza A virus (IAV) causes annual epidemics and occasional pandemics, and is one of the best-characterized human RNA viral pathogens(1). However, a physiologically relevant role for the RNA interference (RNAi) suppressor activity of the IAV non-structural protein 1 (NS1), reported over a decade ago(2), remains unknown(3). Plant and insect viruses have evolved diverse virulence proteins to suppress RNAi as their hosts produce virus-derived small interfering RNAs (siRNAs) that direct specific antiviral defence(4-7) by an RNAi mechanism dependent on the slicing activity of Argonaute proteins (AGOs)(8,9)...
December 5, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27917878/spatiotemporal-control-of-interferon-induced-jak-stat-signalling-and-gene-transcription-by-the-retromer-complex
#14
Daniela Chmiest, Nanaocha Sharma, Natacha Zanin, Christine Viaris de Lesegno, Massiullah Shafaq-Zadah, Vonick Sibut, Florent Dingli, Philippe Hupé, Stephan Wilmes, Jacob Piehler, Damarys Loew, Ludger Johannes, Gideon Schreiber, Christophe Lamaze
Type-I interferons (IFNs) play a key role in the immune defences against viral and bacterial infections, and in cancer immunosurveillance. We have established that clathrin-dependent endocytosis of the type-I interferon (IFN-α/β) receptor (IFNAR) is required for JAK/STAT signalling. Here we show that the internalized IFNAR1 and IFNAR2 subunits of the IFNAR complex are differentially sorted by the retromer at the early endosome. Binding of the retromer VPS35 subunit to IFNAR2 results in IFNAR2 recycling to the plasma membrane, whereas IFNAR1 is sorted to the lysosome for degradation...
December 5, 2016: Nature Communications
https://www.readbyqxmd.com/read/27914803/effectiveness-of-direct-acting-antivirals-in-hepatitis-c-virus-infection-in-haemodialysis-patients
#15
Soraya Abad, Almudena Vega, Diego Rincón, Eduardo Hernández, Evangelina Mérida, Nicolás Macías, Raquel Muñoz, Mónica Milla, Jose Luño, Juan Manuel López-Gómez
Hepatitis C virus (HCV) infection is highly prevalent among patients on haemodialysis and leads to a poorer prognosis compared to patients who do not have said infection. Treatment with interferon and ribavirin is poorly tolerated and there are limited data on the experience with new direct-acting antivirals (DAAs). The aim of this study is to retrospectively analyse the current prevalence of HCV infection and efficacy and safety results with different DAA regimens in the haemodialysis population of 2hospital areas...
November 30, 2016: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/27908830/protective-efficacy-of-fc-targeting-conserved-influenza-virus-m2e-antigen-expressed-by-lactobacillus-plantarum
#16
Wen-Tao Yang, Gui-Lian Yang, Qian Wang, Hai-Bin Huang, Yan-Long Jiang, Chun-Wei Shi, Jian-Zhong Wang, Ke-Yan Huang, Yu-Bei Jin, Chun-Feng Wang
The influenza A (H1N1) virus is a highly contagious acute respiratory disease affecting pigs and humans. This disease causes severe economic loss in many countries, and developing mucosal vaccines is an efficient strategy to control the influenza virus. The neonatal Fc receptor (FcRn) plays an important role in transferring IgG across polarized epithelial cells. In the present study, an oral vaccine was developed using Lactobacillus plantarum to deliver the internal influenza viral protein M2e fused to an IgG Fc fragment...
November 28, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27907166/vaccinia-virus-protein-c6-inhibits-type-i-ifn-signalling-in-the-nucleus-and-binds-to-the-transactivation-domain-of-stat2
#17
Jennifer H Stuart, Rebecca P Sumner, Yongxu Lu, Joseph S Snowden, Geoffrey L Smith
The type I interferon (IFN) response is a crucial innate immune signalling pathway required for defense against viral infection. Accordingly, the great majority of mammalian viruses possess means to inhibit this important host immune response. Here we show that vaccinia virus (VACV) strain Western Reserve protein C6, is a dual function protein that inhibits the cellular response to type I IFNs in addition to its published function as an inhibitor of IRF-3 activation, thereby restricting type I IFN production from infected cells...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27903802/a-protective-role-for-il-1-signaling-during-mouse-adenovirus-type-1-induced-encephalitis
#18
Luiza A Castro-Jorge, Carla Pretto, Asa Smith, Oded Foreman, Kelly E Carnahan, Katherine R Spindler
: IL-1β, an inflammatory cytokine and IL-1 receptor ligand, has diverse activities in the brain. We examined whether IL-1 signaling contributes to the encephalitis observed in mouse adenovirus type 1 (MAV-1) infection, using mice lacking the IL-1 receptor, Il1r1(-/-) Il1r1(-/-) mice had lower survival, higher disruption of the blood-brain barrier (BBB), higher brain viral loads, and higher brain inflammatory cytokines and chemokines than control C57BL/6 mice. We also examined infections of mice defective in IL-1β production (Pycard(-/-)mice) and mice defective in trafficking of TLRs to the endosome (Unc93b1(-/-) mice)...
November 30, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27903277/sequence-diversity-of-dengue-virus-type-2-in-brain-and-thymus-of-infected-interferon-receptor-ko-mice-implications-for-dengue-virulence
#19
Priya Dhole, Emi E Nakayama, Akatsuki Saito, Kriengsak Limkittikul, Supranee Phanthanawiboon, Tatsuo Shioda, Takeshi Kurosu
BACKGROUND: We previously reported that a clinical isolate of dengue virus (DENV) is capable of causing acute-phase systemic infection in mice harboring knockouts of the genes encoding type-I and -II interferon IFN receptors (IFN-α/β/γR KO mice); in contrast, other virulent DENV isolates exhibited slow disease progression in this mice, yielding lethal infection around 20 days post-infection (p.i.). In the present study, we sought to clarify the dynamics of slow disease progression by examining disease progression of a type-2 DENV clinical isolate (DV2P04/08) in mice...
November 30, 2016: Virology Journal
https://www.readbyqxmd.com/read/27902332/inhibition-of-hepatitis-b-virus-replication-by-activation-of-the-cgas-sting-pathway
#20
Jing He, Ruidong Hao, Dan Liu, Xing Liu, Shaoshuai Wu, Shuting Guo, Yuan Wang, Deyin Guo
Cyclic GMP-AMP (cGAMP) synthase (cGAS) senses cytosolic DNA and catalyzes synthesis of the second messenger cGAMP, which activates the downstream signaling adaptor protein STING, leading to the expression of type I interferons. Hepatitis B virus (HBV) is a small DNA virus, and the cGAS-STING pathway may inhibit HBV RNA synthesis and viral assembly in cell culture, but the exact roles of cGAS pathway in the restriction of HBV replication in infection systems remain to be elucidated. In this study, we showed that the replication of HBV was significantly inhibited both in cell culture and in vivo in a mouse model when the cGAS-STING pathway was activated by dsDNA or cGAMP...
October 31, 2016: Journal of General Virology
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