88 results match your criteria mda5 tbk1


Host protein, HSP90β, antagonizes IFN-β signaling pathway and facilitates the proliferation of encephalomyocarditis virus in vitro.

Virus Res 2021 Aug 21;305:198547. Epub 2021 Aug 21.

Key Laboratory of Biotechnology and Bioengineering of State Ethnic Affairs Commission, Biomedical Research Center, Northwest Minzu University, Lanzhou 730030, China; Gansu Tech Innovation Center of Animal Cell, Biomedical Research Center, Northwest Minzu University, Lanzhou, China. Electronic address:

Encephalomyocarditis virus (EMCV) is a small, non-enveloped, single stranded RNA virus which infects a wide variety of mammalian species, and has zoonotic importance. Many host proteins are known to regulate EMCV proliferation by interacting with its structural or nonstructural proteins, but the regulatory role and mechanism of heat shock protein 90β (HSP90β), in EMCV infection has not been reported yet. Here, we report that overexpression of HSP90β significantly promotes the growth and proliferation of EMCV in vitro. Read More

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Human TBK1 deficiency leads to autoinflammation driven by TNF-induced cell death.

Cell 2021 Aug 6;184(17):4447-4463.e20. Epub 2021 Aug 6.

Center for Inborn Errors of Immunity, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. Electronic address:

TANK binding kinase 1 (TBK1) regulates IFN-I, NF-κB, and TNF-induced RIPK1-dependent cell death (RCD). In mice, biallelic loss of TBK1 is embryonically lethal. We discovered four humans, ages 32, 26, 7, and 8 from three unrelated consanguineous families with homozygous loss-of-function mutations in TBK1. Read More

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Duck Tembusu Virus Infection Promotes the Expression of Duck Interferon-Induced Protein 35 to Counteract RIG-I Antiviral Signaling in Duck Embryo Fibroblasts.

Front Immunol 2021 15;12:711517. Epub 2021 Jul 15.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Duck Tembusu virus (DTMUV) is an emerging pathogenic flavivirus that has caused a substantial drop in egg production and severe neurological disorders in domestic waterfowl. Several studies have revealed that viral proteins encoded by DTMUV antagonize host IFN-mediated antiviral responses to facilitate virus replication. However, the role of host gene expression regulated by DTMUV in innate immune evasion remains largely unknown. Read More

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RIG-I-Like Receptor-Mediated Recognition of Viral Genomic RNA of Severe Acute Respiratory Syndrome Coronavirus-2 and Viral Escape From the Host Innate Immune Responses.

Front Immunol 2021 25;12:700926. Epub 2021 Jun 25.

Department of Immunology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

RIG-I-like receptors (RLR), RIG-I and MDA5, are cytoplasmic viral RNA sensors that recognize viral double-stranded RNAs and trigger signals to induce antiviral responses, including type I interferon production. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused the coronavirus disease 2019 pandemic. However, the RLR role in innate immune response to SARS-CoV-2 has not been fully elucidated. Read More

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Bovine Papillomavirus E5 Oncoprotein Interacts With TRIM25 and Hampers Antiviral Innate Immune Response Mediated by RIG-I-Like Receptors.

Front Immunol 2021 10;12:658762. Epub 2021 Jun 10.

Dipartimento di Medicina Veterinaria e Produzioni Animali, Università degli Studi di Napoli Federico II, Napoli, Italy.

Persistent infection and tumourigenesis by papillomaviruses (PVs) require viral manipulation of various of cellular processes, including those involved in innate immune responses. Herein, we showed that bovine PV (BPV) E5 oncoprotein interacts with a tripartite motif-containing 25 (TRIM25) but not with Riplet in spontaneous BPV infection of urothelial cells of cattle. Statistically significant reduced protein levels of TRIM25, retinoic acid-inducible gene I (RIG-I), and melanoma differentiation-associated gene 5 (MDA5) were detected by Western blot analysis. Read More

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SARS-CoV-2 Membrane Protein Inhibits Type I Interferon Production Through Ubiquitin-Mediated Degradation of TBK1.

Front Immunol 2021 18;12:662989. Epub 2021 May 18.

Laboratory of Emerging Infectious Disease, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen of current COVID-19 pandemic, and insufficient production of type I interferon (IFN-I) is associated with the severe forms of the disease. Membrane (M) protein of SARS-CoV-2 has been reported to suppress host IFN-I production, but the underlying mechanism is not completely understood. In this study, SARS-CoV-2 M protein was confirmed to suppress the expression of IFNβ and interferon-stimulated genes induced by RIG-I, MDA5, IKKϵ, and TBK1, and to inhibit IRF3 phosphorylation and dimerization caused by TBK1. Read More

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Interplay of the ubiquitin proteasome system and the innate immune response is essential for the replication of infectious bronchitis virus.

Arch Virol 2021 Aug 26;166(8):2173-2185. Epub 2021 May 26.

Key Laboratory of Animal Virology of Ministry of Agriculture, Department of Veterinary Medicine, College of Animal Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou, People's Republic of China.

Infectious bronchitis virus (IBV) is the only coronavirus known to infect poultry. The replication and pathogenesis of IBV are poorly understood, mainly because of the unavailability of a robust cell culture system. Here, we report that an active ubiquitin proteasome system (UPS) is necessary for efficient replication of IBV in Vero cells. Read More

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Inhibition of Antiviral Innate Immunity by VP3 via Blocking TBK1-TRAF3 Complex Formation and IRF3 Activation.

mSystems 2021 May 11;6(3). Epub 2021 May 11.

MOA Key Laboratory of Animal Virology, Zhejiang University Center for Veterinary Sciences, Hangzhou, People's Republic of China

The host innate immune system develops various strategies to antagonize virus infection, and the pathogen subverts or evades host innate immunity for self-replication. In the present study, we discovered that infectious bursal disease virus (IBDV) VP3 protein significantly inhibits MDA5-induced beta interferon (IFN-β) expression by blocking IRF3 activation. Binding domain mapping showed that the CC1 domain of VP3 and the residue lysine-155 of tumor necrosis factor receptor-associated factor 3 (TRAF3) are essential for the interaction. Read More

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Lipotoxicity reduces DDX58/Rig-1 expression and activity leading to impaired autophagy and cell death.

Autophagy 2021 May 9:1-19. Epub 2021 May 9.

Institute of Metabolic Disorders, Genesis Biotechnology Group, Hamilton, NJ, USA.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally. NAFLD is a consequence of fat accumulation in the liver leading to lipotoxicity. Increasing evidence has demonstrated the critical role of autophagy in NAFLD. Read More

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SARS-CoV-2 ORF9b antagonizes type I and III interferons by targeting multiple components of the RIG-I/MDA-5-MAVS, TLR3-TRIF, and cGAS-STING signaling pathways.

J Med Virol 2021 09 9;93(9):5376-5389. Epub 2021 May 9.

Key Laboratory for Experimental Teratology of Ministry of Education and Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

The suppression of types I and III interferon (IFN) responses by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contributes to the pathogenesis of coronavirus disease 2019 (COVID-19). The strategy used by SARS-CoV-2 to evade antiviral immunity needs further investigation. Here, we reported that SARS-CoV-2 ORF9b inhibited types I and III IFN production by targeting multiple molecules of innate antiviral signaling pathways. Read More

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September 2021

Viral infection of cells within the tumor microenvironment mediates antitumor immunotherapy via selective TBK1-IRF3 signaling.

Nat Commun 2021 03 25;12(1):1858. Epub 2021 Mar 25.

Department of Neurosurgery, Duke University Medical School, Durham, NC, USA.

Activating intra-tumor innate immunity might enhance tumor immune surveillance. Virotherapy is proposed to achieve tumor cell killing, while indirectly activating innate immunity. Here, we report that recombinant poliovirus therapy primarily mediates antitumor immunotherapy via direct infection of non-malignant tumor microenvironment (TME) cells, independent of malignant cell lysis. Read More

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Uncovering targets of the Leader protease: Linking RNA-mediated pathways and antiviral defense.

Wiley Interdiscip Rev RNA 2021 07 18;12(4):e1645. Epub 2021 Feb 18.

Department of Genome Dynamics and Function, Centro de Biologia Molecular Severo Ochoa, Madrid, Spain.

RNA viruses have developed specialized mechanisms to subvert host RNA-binding proteins (RBPs) favoring their own gene expression. The Leader (L) protein of foot-and-mouth disease virus, a member of the Picornaviridae family, is a papain-like cysteine protease that self-cleaves from the polyprotein. Early in infection, the L protease cleaves the translation initiation factors eIF4GI and eIF4GII, inducing the shutdown of cap-dependent translation. Read More

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The negative regulation of retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) signaling pathway in fish.

Authors:
Ming Xian Chang

Dev Comp Immunol 2021 Jun 4;119:104038. Epub 2021 Feb 4.

State Key Laboratory of Freshwater Ecology and Biotechnology, Key Laboratory of Aquaculture Disease Control, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, China; Innovation Academy for Seed Design, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China. Electronic address:

At each stage of innate immune response, there are stimulatory and inhibitory signals that modulate the strength and character of the response. RIG-I-like receptor (RLR) signaling pathway plays pivotal roles in antiviral innate immune response. Recent studies have revealed the molecular mechanisms that viral infection leads to the activation of RLRs-mediated downstream signaling cascades and the production of type I interferons (IFNs). Read More

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Human Cancer Cells Sense Cytosolic Nucleic Acids Through the RIG-I-MAVS Pathway and cGAS-STING Pathway.

Front Cell Dev Biol 2020 8;8:606001. Epub 2021 Jan 8.

Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China.

Pattern recognition receptors (PRRs) are germline-encoded host sensors of the innate immune system. Some human cancer cells have been reported to express PRRs. However, nucleic acid sensors in human cancers have not been studied in detail. Read More

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January 2021

Chicken optineurin suppresses MDA5-mediated interferon β production.

Poult Sci 2021 Jan 27;100(1):9-18. Epub 2020 Aug 27.

Department of Veterinary Preventive Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, P. R. China; Jiangxi Provincial Key laboratory for Animal Science and Technology, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, P. R. China. Electronic address:

Chicken MDA5 (chMDA5), the essential accepted pattern recognition receptors for detecting cytoplasmic viral RNA in chicken, initiates interferon β (IFN-β) generation. However, there is an incomplete elucidation of regulating chMDA5-mediated IFN-β production. NEMO-related protein, optineurin, was identified as inhibitors of virus triggered IFN-β induction in human or mice. Read More

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January 2021

Encephalomyocarditis Virus Abrogates the Interferon Beta Signaling Pathway via Its Structural Protein VP2.

J Virol 2021 02 24;95(6). Epub 2021 Feb 24.

Key Laboratory of Biotechnology and Bioengineering of State Ethnic Affairs Commission, Biomedical Research Center, Northwest Minzu University, Lanzhou, China

Type I interferon (IFN)-mediated antiviral responses are critical for modulating host-virus responses, and indeed, viruses have evolved strategies to antagonize this pathway. Encephalomyocarditis virus (EMCV) is an important zoonotic pathogen, which causes myocarditis, encephalitis, neurological disease, reproductive disorders, and diabetes in pigs. This study aims to understand how EMCV interacts with the IFN pathway. Read More

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February 2021

Porcine haemagglutinating encephalomyelitis virus deactivates transcription factor IRF3 and limits type I interferon production.

Vet Microbiol 2021 Jan 5;252:108918. Epub 2020 Nov 5.

Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China. Electronic address:

Porcine haemagglutinating encephalomyelitis virus (PHEV) is a member of coronavirus that causes acute infectious disease and high mortality in piglets. The transcription factor IRF3 is a central regulator of type I interferon (IFN) innate immune signalling. Here, we report that PHEV infection of RAW264. Read More

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January 2021

A Novel Transcript Isoform of TBK1 Negatively Regulates Type I IFN Production by Promoting Proteasomal Degradation of TBK1 and Lysosomal Degradation of IRF3.

Front Immunol 2020 30;11:580864. Epub 2020 Sep 30.

State Key Laboratory of Freshwater Ecology and Biotechnology, Key Laboratory of Aquaculture Disease Control, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.

TANK-binding kinase 1 (TBK1), an IKK-related serine/threonine kinase, is pivotal for the induction of antiviral type I interferon (IFN) by TLR and RLR signaling pathways. In a previous study, we demonstrated that TBK1 spliced isoforms (TBK1_tv1 and TBK1_tv2) from zebrafish were dominant negative regulators in the RLR antiviral pathway by targeting the functional TBK1-IRF3 complex formation. In this study, we show that the third TBK1 isoform (namely TBK1_tv3) inhibits zebrafish type I IFN production by promoting TBK1 and IRF3 degradation. Read More

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TLR3/TAK1 signalling regulates rhinovirus-induced interleukin-33 in bronchial smooth muscle cells.

ERJ Open Res 2020 Oct 5;6(4). Epub 2020 Oct 5.

Dept of Experimental Medical Science, Lund University, Lund, Sweden.

Background: Asthma exacerbations are commonly associated with rhinovirus (RV) infection. Interleukin-33 (IL-33) plays an important role during exacerbation by enhancing Type 2 inflammation. Recently we showed that RV infects bronchial smooth muscle cells (BSMCs) triggering production of interferons and IL-33. Read More

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October 2020

Palmitic Acid Promotes Virus Replication in Fish Cell by Modulating Autophagy Flux and TBK1-IRF3/7 Pathway.

Front Immunol 2020 5;11:1764. Epub 2020 Aug 5.

Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, China.

Palmitic acid is the most common saturated fatty acid in animals, plants, and microorganisms. Studies highlighted that palmitic acid plays a significant role in diverse cellular processes and viral infections. Accumulation of palmitic acid was observed in fish cells (grouper spleen, GS) infected with Singapore grouper iridovirus (SGIV). Read More

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Porcine deltacoronavirus (PDCoV) infection antagonizes interferon-λ1 production.

Vet Microbiol 2020 Aug 2;247:108785. Epub 2020 Jul 2.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, the Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. Electronic address:

Porcine deltacoronavirus (PDCoV) is a novel swine enteropathogenic coronavirus that causes watery diarrhea, vomiting and mortality in nursing piglets. Type III interferons (IFN-λs) are the major antiviral cytokines in intestinal epithelial cells, the target cells in vivo for PDCoV. In this study, we found that PDCoV infection remarkably inhibited Sendai virus-induced IFN-λ1 production by suppressing transcription factors IRF and NF-κB in IPI-2I cells, a line of porcine intestinal mucosal epithelial cells. Read More

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Dissecting distinct proteolytic activities of FMDV Lpro implicates cleavage and degradation of RLR signaling proteins, not its deISGylase/DUB activity, in type I interferon suppression.

PLoS Pathog 2020 07 15;16(7):e1008702. Epub 2020 Jul 15.

Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.

The type I interferon response is an important innate antiviral pathway. Recognition of viral RNA by RIG-I-like receptors (RLRs) activates a signaling cascade that leads to type I interferon (IFN-α/β) gene transcription. Multiple proteins in this signaling pathway (e. Read More

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Porcine Deltacoronavirus Accessory Protein NS7a Antagonizes IFN-β Production by Competing With TRAF3 and IRF3 for Binding to IKKε.

Front Cell Infect Microbiol 2020 12;10:257. Epub 2020 Jun 12.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

As an emerging swine enteropathogenic coronavirus, porcine deltacoronavirus (PDCoV) not only causes serious diarrhea in suckling piglets but also possesses the potential for cross-species transmission, which has sparked growing interest when studying this emerging virus. We previously identified a novel accessory protein NS7a encoded by PDCoV; however, the function of NS7a was not resolved. In this study, we demonstrated that PDCoV NS7a is an interferon antagonist. Read More

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The Andes Orthohantavirus NSs Protein Antagonizes the Type I Interferon Response by Inhibiting MAVS Signaling.

J Virol 2020 06 16;94(13). Epub 2020 Jun 16.

Laboratorio de Virología Molecular, Instituto Milenio de Inmunología e Inmunoterapia, Departamento de Enfermedades Infecciosas e Inmunología Pediátrica, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

The small messenger RNA (SmRNA) of the (ANDV), a rodent-borne member of the family of viruses of the order, encodes a multifunctional nucleocapsid (N) protein and for a nonstructural (NSs) protein of unknown function. We have previously shown the expression of the ANDV-NSs, but only in infected cell cultures. In this study, we extend our early findings by confirming the expression of the ANDV-NSs protein in the lungs of experimentally infected golden Syrian hamsters. Read More

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Binding of Duck Tembusu Virus Nonstructural Protein 2A to Duck STING Disrupts Induction of Its Signal Transduction Cascade To Inhibit Beta Interferon Induction.

J Virol 2020 04 16;94(9). Epub 2020 Apr 16.

Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang District, Chengdu City, Sichuan Province, China

Duck Tembusu virus (DTMUV), which is similar to other mosquito-borne flaviviruses that replicate well in most mammalian cells, is an emerging pathogenic flavivirus that has caused epidemics in egg-laying and breeding waterfowl. Immune organ defects and neurological dysfunction are the main clinical symptoms of DTMUV infection. Preinfection with DTMUV makes the virus impervious to later interferon (IFN) treatment, revealing that DTMUV has evolved some strategies to defend against host IFN-dependent antiviral responses. Read More

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Endogenous Retrovirus Activation as a Key Mechanism of Anti-Tumor Immune Response in Radiotherapy.

Radiat Res 2020 04 19;193(4):305-317. Epub 2020 Feb 19.

Department of Pharmacology and Cancer Biology, Duke University Graduate School, Durham, North Carolina.

The generation of DNA double-strand breaks has historically been taught as the mechanism through which radiotherapy kills cancer cells. Recently, radiation-induced cytosolic DNA release and activation of the cGAS/STING pathway, with ensuing induction of interferon secretion and immune activation, have been recognized as important mechanisms for radiation-mediated anti-tumor efficacy. Here we demonstrate that radiation-induced activation of endogenous retroviruses (ERVs) also plays a major role in regulating the anti-tumor immune response during irradiation. Read More

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Binding of the Duck Tembusu Virus Protease to STING Is Mediated by NS2B and Is Crucial for STING Cleavage and for Impaired Induction of IFN-β.

J Immunol 2019 12 8;203(12):3374-3385. Epub 2019 Nov 8.

Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang District, Chengdu 611130, Sichuan, China;

Duck Tembusu virus (DTMUV) is a newly emerged causative agent of avian disease. The protease-dependent immune evasion of flaviviruses has been reported; however, the molecular details of this process are unclear. In this study, we found that DTMUV nonstructural protein 2B-3, a NS2B3 protease, can inhibit IFN-β production. Read More

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December 2019

Hepatitis C Virus Infection Is Inhibited by a Noncanonical Antiviral Signaling Pathway Targeted by NS3-NS4A.

J Virol 2019 12 13;93(23). Epub 2019 Nov 13.

Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA

The hepatitis C virus (HCV) NS3-NS4A protease complex is required for viral replication and is the major viral innate immune evasion factor. NS3-NS4A evades antiviral innate immunity by inactivating several proteins, including MAVS, the signaling adaptor for RIG-I and MDA5, and Riplet, an E3 ubiquitin ligase that activates RIG-I. Here, we identified a Tyr-16-Phe (Y16F) change in the NS4A transmembrane domain that prevents NS3-NS4A targeting of Riplet but not MAVS. Read More

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December 2019

Azithromycin Protects against Zika virus Infection by Upregulating virus-induced Type I and III Interferon Responses.

Antimicrob Agents Chemother 2019 Sep 16. Epub 2019 Sep 16.

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.

Azithromycin (AZM) is a widely used antibiotic, with additional antiviral and anti-inflammatory properties that remain poorly understood. Although Zika virus (ZIKV) poses a significant threat to global health, there are currently no vaccines or effective therapeutics against it. Herein, we report that AZM effectively suppresses ZIKV infection by targeting a late stage in the viral life cycle. Read More

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September 2019

Middle East Respiratory Syndrome Coronavirus-Encoded Accessory Proteins Impair MDA5-and TBK1-Mediated Activation of NF-κB.

J Microbiol Biotechnol 2019 Aug;29(8):1316-1323

Korea Zoonosis Research Institute, Genetic Engineering Research Institute and Department of Bioactive Material Science, Chonbuk National University, Jeongju 54531, Republic of Korea.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging coronavirus which is zoonotic from bats and camels. Its infection in humans can be fatal especially in patients with preexisting conditions due to smoking and chronic obstructive pulmonary disease (COPD). Among the 25 proteins encoded by MERS-CoV, 5 accessory proteins seem to be involved in viral evasion of the host immune responses. Read More

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