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Interferons and viral infections

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https://www.readbyqxmd.com/read/28822811/reduced-dynamic-range-of-antiviral-innate-immune-responses-in-aging
#1
REVIEW
Ryan D Molony, Anna Malawista, Ruth R Montgomery
The worldwide population aged≥65years is increasing and the average life span is expected to increase another 10years by 2050. This extended lifespan is associated with a progressive decline in immune function and a paradoxical state of low-grade, chronic inflammation that may contribute to susceptibility to viral infection, and reduced responses to vaccination. Here we review the effects of aging on innate immune responses to viral pathogens including elements of recognition, signaling, and production of inflammatory mediators...
August 16, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28822807/spontaneous-activation-of-a-mavs-dependent-antiviral-signaling-pathway-determines-high-basal-interferon-%C3%AE-expression-in-cardiac-myocytes
#2
Efraín E Rivera-Serrano, Nicole DeAngelis, Barbara Sherry
Viral myocarditis is a leading cause of sudden death in young adults as the limited turnover of cardiac myocytes renders the heart particularly vulnerable to viral damage. Viruses induce an antiviral type I interferon (IFN-α/β) response in essentially all cell types, providing an immediate innate protection. Cardiac myocytes express high basal levels of IFN-β to help pre-arm them against viral infections, however the mechanism underlying this expression remains unclear. Using primary cultures of murine cardiac and skeletal muscle cells, we demonstrate here that the mitochondrial antiviral signaling (MAVS) pathway is spontaneously activated in unstimulated cardiac myocytes but not cardiac fibroblasts or skeletal muscle cells...
August 16, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28820758/lack-of-association-between-interleukin-28b-polymorphism-and-vertical-transmission-of-hepatitis-c
#3
Afrodite Psaros Einberg, Ann-Sofi Duberg, Olga Filipovich, Jessica Nyström, Anton Zhirkov, Erwin Daniel Brenndörfer, Lars Frelin, Elena Rukoiatkina, Yuriy Lobzin, Matti Sällberg, Björn Fischler, Anton Lutckii
OBJECTIVES: Single genetic nucleotide polymorphism (rs12979860) near the gene for Interleukin 28B (IL28B), is known to be of importance for frequency of spontaneous clearance and treatment outcome in interferon based therapies in patients with hepatitis C virus (HCV) infection. The aim of this study was to investigate if IL28B polymorphism in children and/or their mothers plays a role in vertical transmission of HCV (HCV-VT). METHODS: Plasma samples from 59 infected women, 76 uninfected children born to infected mothers, and 47 children with known vertically transmitted HCV infection, were analysed for IL28B polymorphism and classified by the IL28B genotype (C/C, C/T and T/T) as well as by viral genotype...
August 17, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28818789/immune-mechanisms-of-respiratory-viral-infections-in-asthma
#4
REVIEW
Hugo A Farne, Sebastian L Johnston
The more severe pathology respiratory viral infections produce in asthma sufferers is a result of a dysregulated immune response. Excess type 2 inflammation is a well-described feature of virally induced asthma exacerbations, with growing evidence that production of antiviral interferons may also be impaired. However, the mechanisms underlying these are little understood. This review summarizes the current understanding and recent discoveries of the cellular and molecular events that follow viral infections in asthma...
August 14, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28818749/a-conjugate-protein-containing-hiv-tat-isg20-and-a-prrsv-polymerase-binding-inhibits-prrsv-replication-and-may-be-a-novel-therapeutic-platform
#5
Ke Liu, Yuming Li, Bin Zhou, Feifei Wang, Beili Huan, Donghua Shao, Jianchao Wei, Yafeng Qiu, Beibei Li, Yingjuan Qian, Yong-Sam Jung, Denian Miao, Guangzhi Tong, Zhiyong Ma
Porcine Reproductive and Respiratory Syndrome (PRRS), which is caused by Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection, has caused substantial economic losses for the global swine industry. To date, there are limited commercially available measures to control the spread of PRRSV. The available vaccines are unstable and there is no anti-PRRSV therapeutic available. Therefore, this study designed a novel recombinant antiviral protein that included a novel polypeptide that binds to the PRRSV polymerase (p9), the transduction ability of the HIV TAT, and the nucleotide degradation activity of interferon stimulated gene 20 (ISG20)...
August 10, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28818572/ribavirin-inhibits-zika-virus-zikv-replication-in-vitro-and-suppresses-viremia-in-zikv-infected-stat1-deficient-mice
#6
Naganori Kamiyama, Ryusuke Soma, Shinya Hidano, Kei Watanabe, Hiroshi Umekita, Chiaki Fukuda, Kaori Noguchi, Yoshiko Gendo, Takashi Ozaki, Akira Sonoda, Nozomi Sachi, Lucky Ronald Runtuwene, Yumako Miura, Etsuro Matsubara, Shigeru Tajima, Tomohiko Takasaki, Yuki Eshita, Takashi Kobayashi
Zika fever, a mosquito-borne infectious disease caused by Zika virus (ZIKV), is an epidemic disease for which no effective therapy has been established. The recent outbreaks of ZIKV in Brazil and French Polynesia have been linked to a considerable increase in the incidence of fetal microcephaly and other diseases such as Guillain-Barre syndrome. Because there is currently no specific therapy or vaccine, the early exploitation of a method to prevent expansion of ZIKV is a high priority. To validate commonly used antiviral drugs, we evaluated the effect of ribavirin, a drug used to treat hepatitis C with interferon-β (IFN-β), on ZIKV replication...
August 14, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28815344/long-term-survival-after-hematopoietic-stem-cell-transplantation-for-complete-stat1-deficiency
#7
Samuele Naviglio, Elena Soncini, Donatella Vairo, Arnalda Lanfranchi, Raffaele Badolato, Fulvio Porta
PURPOSE: Complete signal transducer and activator of transcription 1 (STAT1) deficiency is a rare autosomal recessive condition characterized by impairment of intracellular signaling from both type I and type II interferons (IFN). Affected patients are prone to early severe mycobacterial and viral infections, which usually result in death before 18 months of age. We previously reported a patient affected by complete STAT1 deficiency who underwent hematopoietic stem cell transplantation (HSCT)...
August 16, 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28815217/deletion-of-cytoplasmic-double-stranded-rna-sensors-does-not-uncover-viral-small-interfering-rna-production-in-human-cells
#8
Susan Schuster, Lotte E Tholen, Gijs J Overheul, Frank J M van Kuppeveld, Ronald P van Rij
Antiviral immunity in insects and plants is mediated by the RNA interference (RNAi) pathway in which viral long double-stranded RNA (dsRNA) is processed into small interfering RNAs (siRNAs) by Dicer enzymes. Although this pathway is evolutionarily conserved, its involvement in antiviral defense in mammals is the subject of debate. In vertebrates, recognition of viral RNA induces a sophisticated type I interferon (IFN)-based immune response, and it has been proposed that this response masks or inhibits antiviral RNAi...
July 2017: MSphere
https://www.readbyqxmd.com/read/28814517/zinc-salts-block-hepatitis-e-virus-replication-by-inhibiting-the-activity-of-viral-rna-dependent-rna-polymerase
#9
Nidhi Kaushik, Chandru Subramani, Saumya Anang, Rajagopalan Muthumohan, Shalimar, Baibaswata Nayak, C T Ranjith-Kumar, Milan Surjit
Hepatitis E virus (HEV) causes an acute, self limiting hepatitis in normal individuals and leads to chronic disease in immunocompromised individuals. HEV infection in pregnant women results in a more severe outcome, with the mortality rate going upto 30%. Though the virus usually causes sporadic infection, epidemics have been reported in developing and resource starved countries. No specific anti-viral exists against HEV. A combination of interferon and ribavirin therapy has been used to control the disease with some success...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28813716/no-correlation-of-the-disease-severity-of-influenza-a-virus-infection-with-the-rs12252-polymorphism-of-the-interferon-induced-transmembrane-protein-3-gene
#10
Yong-Chan Kim, Byung-Hoon Jeong
The 2009 H1N1 influenza pandemic, which involved a more pathogenic virus than seasonal influenza viruses, rapidly spread around the world and caused many deaths in humans. The members of the interferon-induced transmembrane (IFITM) protein family prevent viral replication and are crucial for defending the host cell against influenza A virus (IAV). Several studies suggest that the CC genotype at the single nucleotide polymorphism (SNP) rs12252 of IFITM3 confers a genetic predisposition to pandemic influenza A in Europeans and Han Chinese, although one study in a British cohort failed to show an association...
August 17, 2017: Intervirology
https://www.readbyqxmd.com/read/28811492/interferon-alpha-treatment-rapidly-clears-hepatitis-e-virus-infection-in-humanized-mice
#11
Martijn D B van de Garde, Suzan D Pas, Gertine W van Oord, Lucio Gama, Youkyung Choi, Robert A de Man, Andre Boonstra, Thomas Vanwolleghem
Antiviral treatment options for chronic Hepatitis E Virus (HEV) infections are limited and immunological determinants of viral persistence remain largely unexplored. We studied the antiviral potency of pegylated interferon-α (pegIFNα) against HEV infections in humanized mice and modelled intrahepatic interferon stimulated gene (ISG) responses. Human gene expression levels in humanized mouse livers were analyzed by qPCR and Nanostring. Human CXCL10 was measured in mouse serum. HEV genotype 3 (gt3) infections were cleared from liver and feces within 8 pegIFNα doses in all mice and relapsed after a single pegIFNα injection in only half of treated animals...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811340/type-iii-interferon-mediated-signaling-is-critical-for-controlling-live-attenuated-yellow-fever-virus-infection-in-vivo
#12
Florian Douam, Yentli E Soto Albrecht, Gabriela Hrebikova, Evita Sadimin, Christian Davidson, Sergei V Kotenko, Alexander Ploss
Yellow fever virus (YFV) is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β) signaling and type II interferon (IFN-γ) signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28810265/viral-retinopathy-in-experimental-models-of-zika-infection
#13
Zhenyang Zhao, Matthew Yang, Sasha R Azar, Lynn Soong, Scott C Weaver, Jiaren Sun, Yan Chen, Shannan L Rossi, Jiyang Cai
Purpose: Emerging evidence has shown that both congenital and adult Zika virus (ZIKV) infection can cause eye diseases. The goals of the current study were to explore mechanisms and pathophysiology of ZIKV-induced eye defects. Methods: Wild-type or A129 interferon type I receptor-deficient mice were infected by either FSS13025 or Mex1-7 strain of ZIKV. Retinal histopathology was measured at different time points after infection. The presence of viral RNA and protein in the retina was determined by in situ hybridization and immunofluorescence staining, respectively...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28808968/cgamp-quantification-in-virus-infected-human-monocyte-derived-cells-by-hplc-coupled-tandem-mass-spectrometry
#14
Jennifer Paijo, Volkhard Kaever, Ulrich Kalinke
Upon virus infection, cells of the innate immune system such as dendritic cells and macrophages can mount type I interferon (IFN-I) responses that restrict viral dissemination. To inform host cells of virus infection, detection of cytosolic DNA is one important mechanism. Inappropriate sensing of endogenous DNA and subsequent induction of IFN-I responses can also cause autoimmunity, highlighting the need to tightly regulate DNA sensing. The cyclic GMP-AMP synthase (cGAS) was recently identified to be the major sensor of cytosolic DNA that triggers IFN-I expression...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808967/purification-of-cyclic-gmp-amp-from-viruses-and-measurement-of-its-activity-in-cell-culture
#15
Alice Mayer, Jonathan Maelfait, Anne Bridgeman, Jan Rehwinkel
Sensing of cytoplasmic DNA by cGAS is essential for the initiation of immune responses against several viruses. cGAS also plays important roles in some autoinflammatory and autoimmune diseases and may be involved in immune responses targeting cancer cells. Once activated, cGAS catalyzes the formation of the di-nucleotide 2'-3'-cyclic GMP-AMP (cGAMP), which propagates a signaling cascade leading to the production of type I interferons (IFNs). Interestingly, cGAMP is incorporated into enveloped viruses and is transferred to newly infected cells by virions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28807557/the-role-of-toll-like-receptor-3-in-chronic-contact-hypersensitivity-induced-by-repeated-elicitation
#16
Risa Yasuike, Risa Tamagawa-Mineoka, Mayumi Ueta, Naomi Nakamura, Shigeru Kinoshita, Norito Katoh
BACKGROUND: Accumulating evidence suggests that Toll-like receptor (TLR)-3 signaling is involved in non-infectious immune and inflammatory reactions as well as in viral infections. The skin of patients with atopic dermatitis (AD) is often infected with virus and bacteria, leading to the aggravation of atopic symptoms. These findings suggest TLR3 signaling may be involved in the pathogenesis of AD, but the exact role of TLR3 in AD remains to be defined. OBJECTIVE: The purpose of this study was to investigate the role of TLR3 in chronic contact hypersensitivity reactions induced by repeated elicitation, resembling the features of AD...
August 4, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28805681/influenza-virus-infection-interferon-response-viral-counter-response-and-apoptosis
#17
REVIEW
Jung Min Shim, Jinhee Kim, Tanel Tenson, Ji-Young Min, Denis E Kainov
Human influenza A viruses (IAVs) cause global pandemics and epidemics, which remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral outbreaks, new treatments are urgently needed. Developing new virus control modalities requires better understanding of virus-host interactions. Here, we describe how IAV infection triggers cellular apoptosis and how this process can be exploited towards the development of new therapeutics, which might be more effective than the currently available anti-influenza drugs...
August 12, 2017: Viruses
https://www.readbyqxmd.com/read/28801732/evaluation-of-the-relationship-between-alopecia-areata-and-viral-antigen-exposure
#18
Christopher T Richardson, Matthew S Hayden, Elaine S Gilmore, Brian Poligone
BACKGROUND: Alopecia areata (AA) is an autoimmune disease characterized by non-scarring alopecia with T-cell infiltration at the affected hair follicle. OBJECTIVE: Our aim was to study the potential link between hepatitis B virus (HBV) antigen exposure and AA. METHODS: Two pediatric patients with AA following hepatitis B vaccination were identified in a general dermatology clinic. A bioinformatics analysis and an electronic medical record (EMR) database query were performed at the University of Rochester Medical Center to identify patients with AA, coexisting viral infections, vaccinations, or interferon (IFN) therapy in order to determine if the presence of AA and these conditions was higher than in AA patients without these associated conditions or therapy...
August 11, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28801534/cgas-is-activated-by-dna-in-a-length-dependent-manner
#19
Stefanie Luecke, Andreas Holleufer, Maria H Christensen, Kasper L Jønsson, Gerardo A Boni, Lambert K Sørensen, Mogens Johannsen, Martin R Jakobsen, Rune Hartmann, Søren R Paludan
Cytosolic DNA stimulates innate immune responses, including type I interferons (IFN), which have antiviral and immunomodulatory activities. Cyclic GMP-AMP synthase (cGAS) recognizes cytoplasmic DNA and signals via STING to induce IFN production. Despite the importance of DNA in innate immunity, the nature of the DNA that stimulates IFN production is not well described. Using low DNA concentrations, we show that dsDNA induces IFN in a length-dependent manner. This is observed over a wide length-span of DNA, ranging from the minimal stimulatory length to several kilobases, and is fully dependent on cGAS irrespective of DNA length...
August 10, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28800954/a-tim-3-oligonucleotide-aptamer-enhances-t-cell-functions-and-potentiates-tumor-immunity-in-mice
#20
Tal Gefen, Iris Castro, Darija Muharemagic, Yvonne Puplampu-Dove, Shradha Patel, Eli Gilboa
T cell immunoglobulin-3 (TIM-3) is a negative regulator of interferon-γ (IFN-γ) secreting CD4(+) T cells and CD8(+) T cytotoxic cells. Recent studies have highlighted the role of TIM-3 as an important mediator of CD8(+) T cell exhaustion in the setting of chronic viral infections and cancer. In murine tumor models, antibody blockade of TIM-3 with anti-TIM-3 antibodies as monotherapy has no or minimal antitumor activity, suggesting that TIM-3 signaling exerts an accessory or amplifying effect in keeping immune responses in check...
August 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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