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Pei-Hui Wang, Sin-Yee Fung, Wei-Wei Gao, Jian-Jun Deng, Yun Cheng, Vidyanath Chaudhary, Kit-San Yuen, Ting-Hin Ho, Ching-Ping Chan, Yan Zhang, Kin-Hang Kok, Wanling Yang, Chi-Ping Chan, Dong-Yan Jin
STING is a core adaptor in innate nucleic acid sensing in mammalian cells, on which different sensing pathways converge to induce type I interferon (IFN) production. Particularly, STING is activated by 2'3'-cGAMP, a cyclic dinucleotide containing mixed phosphodiester linkages and produced by cytoplasmic DNA sensor cGAS. Here, we reported on a novel transcript isoform of STING designated STING-β that dominantly inhibits innate nucleic acid sensing. STING-β without transmembrane domains was widely expressed at low levels in various human tissues and viral induction of STING-β correlated inversely with IFN-β production...
March 14, 2018: Nucleic Acids Research
Hong-Jie Li, Dong-Sheng Gao, Yong-Tao Li, Yong-Sheng Wang, Hong-Ying Liu, Jun Zhao
Porcine epidemic diarrhea virus (PEDV), a member of the Coronaviridae family, causes acute diarrhea, vomiting, dehydration, and high mortality rates in neonatal piglets. Severe outbreaks of PEDV variants have re-emerged in Asia and North America since 2010, causing tremendous economic losses to the swine industry. The lack of effective therapeutic treatment promotes the research for new antivirals. Lithium chloride (LiCl) has been reported as a potential antiviral drug for certain viruses. In this study, the antiviral effect of LiCl on PEDV in Vero cells was evaluated...
March 5, 2018: Research in Veterinary Science
Mitchell R White, Ruth Kandel, I-Ni Hsieh, Xavier De Luna, Kevan L Hartshorn
Recent studies have shown that the Alzheimer's associated β-amyloid protein (βA) can inhibit growth of bacteria, fungi and viruses. We reported that the 42 amino acid βA protein inhibits replication of seasonal and pandemic strains of H3N2 and H1N1 influenza A virus (IAV) in vitro and modulates activation of neutrophils and monocytes exposed IAV. We here show that fragments composed of the N and C terminal domain of βA42, including βA22-42 and the 8 amino acid βA35-42, retain viral neutralizing and viral aggregating activity, whereas fragments lacking the C-terminal amino acids 41 and 42 (e...
2018: PloS One
Matthew J Murray, Nicholas E Peters, Matthew B Reeves
The host cell represents a hostile environment that viruses must counter in order to establish infection. Human cytomegalovirus (HCMV) is no different and encodes a multitude of functions aimed at disabling, re-directing or hijacking cellular functions to promulgate infection. However, during the very early stages of infection the virus relies on the outcome of interactions between virion components, cell surface receptors and host signalling pathways to promote an environment that supports infection. In the context of latent infection-where the virus establishes an infection in an absence of many gene products specific for lytic infection-these initial interactions are crucial events...
March 16, 2018: Pathogens
Carolina de la Guardia, David E Stephens, Hang T Dang, Mario Quijada, Oleg V Larionov, Ricardo Lleonart
Dengue virus causes dengue fever, a debilitating disease with an increasing incidence in many tropical and subtropical territories. So far, there are no effective antivirals licensed to treat this virus. Here we describe the synthesis and antiviral activity evaluation of two compounds based on the quinoline scaffold, which has shown potential for the development of molecules with various biological activities. Two of the tested compounds showed dose-dependent inhibition of dengue virus serotype 2 in the low and sub micromolar range...
March 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Timothy J Green, Peter Speck
The Pacific oyster, Crassostrea gigas , is becoming a valuable model for investigating antiviral defense in the Lophotrochozoa superphylum. In the past five years, improvements to laboratory-based experimental infection protocols using Ostreid herpesvirus I (OsHV-1) from naturally infected C. gigas combined with next-generation sequencing techniques has revealed that oysters have a complex antiviral response involving the activation of all major innate immune pathways. Experimental evidence indicates C. gigas utilizes an interferon-like response to limit OsHV-1 replication and spread...
March 16, 2018: Viruses
Brice Jegado, Chloé Journo, Renaud Mahieux
No abstract text is available yet for this article.
March 2018: Médecine Sciences: M/S
Alessandra Maria Mont Alverne Pierre, Ana Cristina de Castro Amaral Feldner, Roberto José de Carvalho Filho, Edmundo Pessoa de Almeida Lopes, Michele Soares Gomes Gouvea, João Renato Rebello Pinho, Claudia Teresa Carvente, Christini Takemi Emori, Genimari Arruda da Silva, Maria Lúcia Cardoso Gomes Ferraz
INTRODUCTION: Hepatitis B virus infection is an important cause of liver disease in hemodialysis patients and renal transplant recipients. Hepatitis Delta virus is a defective virus transmitted by the same route of hepatitis B virus, which requires the helper function of hepatitis B virus. Data about hepatitis B virus/hepatitis delta virus coinfection are scarce and there are no studies regarding the coinfection among hemodialysis patients and renal transplant in our country. OBJECTIVE: This study aimed to investigate the prevalence of hepatitis delta virus infection among hemodialysis patients and renal transplant recipients...
March 2018: International Journal of Artificial Organs
Adel Abdel-Moneim, Alaa Aboud, Mohamed Abdel-Gabbar, Mohamed Zanaty, Mohamed Ramadan
BACKGROUND: The current standard of care for patients with chronic hepatitis C virus (HCV) infection is a combination of direct-acting antiviral agents (DAAs). However, rare clinical trials have been reported on the combination regimen of sofosbuvir (SOF) with ombitasvir, paritaprevir, and ritonavir (OBV/PTV/r) plus ribavirin (RBV) for treated patients with HCV genotype 4 (GT4) infection. AIMS: To clarify the retreatment efficacy and safety of the recent regimen, SOF with OBV/PTV/r + RBV, for chronic HCV GT4-experienced patients who failed treatment with DAA-based regimens...
March 15, 2018: Digestive Diseases and Sciences
Young-A Heo, Emma D Deeks
A fixed-dose combination of the hepatitis C virus (HCV) NS5B polymerase inhibitor sofosbuvir, the HCV NS5A inhibitor velpatasvir and the HCV NS3/4A protease inhibitor voxilaprevir (sofosbuvir/velpatasvir/voxilaprevir; Vosevi® ) is approved in the EU for the treatment of chronic HCV genotype 1, 2, 3, 4, 5 or 6 infection in adults. In the phase III POLARIS trials, in patients who had HCV genotype 1-6 infection with or without compensated cirrhosis, overall rates of sustained virological response at 12 weeks post-treatment (SVR12 ) with sofosbuvir/velpatasvir/voxilaprevir were high after 8 weeks of treatment in direct-acting antiviral (DAA)-naïve patients and 12 weeks of treatment in DAA-experienced patients...
March 15, 2018: Drugs
D Czock, V Schwenger, D Kindgen-Milles, M Joannidis, S John, M Schmitz, A Jörres, A Zarbock, M Oppert, J T Kielstein, C Willam
BACKGROUND: Many anti-infective drugs require dose adjustments in critically ill patients with acute kidney injury (AKI) and renal replacement therapy, in order to achieve adequate therapeutic drug concentrations. OBJECTIVES: The fundamental pharmacokinetic and pharmacodynamic principles of drug dose adjustment are presented. Recommendations on anti-infective drug dosage in intensive care are provided. MATERIALS AND METHODS: We established dose recommendations of selected anti-infective drugs based on information in the summary of product characteristics, published studies and recommendations, pharmacokinetic and pharmacodynamic considerations, and the experience and expert opinion of the authors...
March 15, 2018: Medizinische Klinik, Intensivmedizin und Notfallmedizin
Lei Zhang, Jie Ren, Peidian Shi, Dong Lu, Chengxue Zhao, Yanxin Su, Lilin Zhang, Jinhai Huang
B4GALT5, also known as β-1, 4 galactosyltransferase V, is one of the members of β-1, 4 galactosyltransferase gene (B4GALT) family, which was concerned with embryonic development, tumor generation, other malignant diseases. In this study, we firstly cloned porcine B4GALT (pB4GALT5) from porcine alveolar macrophages, and predicted the structural domain and function of seven porcine β-1, 4 galactosyltransferase (I-VII) based on transcriptome analysis of PRRSV infected cells. Additionally, the upregulated porcine B4GALT5 expression was detected from PRRSV infected porcine alveolar macrophage (PAM) cells...
2018: Frontiers in Cellular and Infection Microbiology
Piera Valenti, Luigi Rosa, Daniela Capobianco, Maria Stefania Lepanto, Elisa Schiavi, Antimo Cutone, Rosalba Paesano, Paola Mastromarino
The innate defense system of the female mucosal genital tract involves a close and complex interaction among the healthy vaginal microbiota, different cells, and various proteins that protect the host from pathogens. Vaginal lactobacilli and lactoferrin represent two essential actors in the vaginal environment. Lactobacilli represent the dominant bacterial species able to prevent facultative and obligate anaerobes outnumber in vaginal microbiota maintaining healthy microbial homeostasis. Several mechanisms underlie the protection exerted by lactobacilli: competition for nutrients and tissue adherence, reduction of the vaginal pH, modulation of immunity, and production of bioactive compounds...
2018: Frontiers in Immunology
Andrea Galli, Helene Mens, Judith M Gottwein, Jan Gerstoft, Jens Bukh
Ribavirin (RBV) is a broad-spectrum antiviral active against a wide range of RNA viruses. Despite having been used for decades in the treatment of chronic hepatitis C virus (HCV) infection, the precise mechanism of action of RBV is unknown. In other viruses, it inhibits propagation by increasing the rate of G-to-A and C-to-U transitions. Here, we utilized the J6/JFH1 HCV cell-culture system to investigate whether RBV inhibits HCV through the same mechanism. Infected Huh7.5 cells were treated with increasing concentrations of RBV or its phosphorylated forms...
March 15, 2018: Scientific Reports
Jiantao Zhang, Yanmei Hu, Christopher Foley, Yuanxiang Wang, Rami Musharrafieh, Shuting Xu, Yongtao Zhang, Chunlong Ma, Christopher Hulme, Jun Wang
Influenza viruses are respiratory pathogens that are responsible for seasonal influenza and sporadic influenza pandemic. The therapeutic efficacy of current influenza vaccines and small molecule antiviral drugs is limited due to the emergence of multidrug-resistant influenza viruses. In response to the urgent need for the next generation of influenza antivirals, we utilized a fast-track drug discovery platform by exploring multi-component reaction products for antiviral drug candidates. Specifically, molecular docking was applied to screen a small molecule library derived from the Ugi-azide four-component reaction methodology for inhibitors that target the influenza polymerase PAC -PB1N interactions...
March 15, 2018: Scientific Reports
Aida Siyahian, Saad Ullah Malik, Adeela Mushtaq, Carol L Howe, Aneela Majeed, Tirdad Zangeneh, Samar Iftikhar, Shahid Habib, Umar Zahid, Irbaz Bin Riaz, Zabih Warraich, Warda Faridi, Faiz Anwer
Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are at a very high risk of hepatitis B virus reactivation (HBVr). Lamivudine is commonly used as prophylaxis against HBVr in high risk patients undergoing allo-HSCT. Unfortunately, its efficacy is diminishing due to the development of HBV mutant drug resistant strains. With the availability of newer antiviral agents like Entecavir, Telbivudine, Adefovir and Tenofovir, it is important to assess their role in HBVr prophylaxis. A comprehensive search of seven databases was performed to evaluate efficacy of antiviral prophylaxis against HBVr in allo-HSCT patients (PubMed/Medline, Embase, Scopus, Cochrane Library, Web of Science, CINAHL, and ClinicalTrials...
March 12, 2018: Biology of Blood and Marrow Transplantation
Liping Qian, Yibo Zuo, Wenjun Deng, Ying Miao, Jin Liu, Yukang Yuan, Tingting Guo, Liting Zhang, Jun Jin, Jun Wang, Hui Zheng
Type-I interferons (IFN-I) are widely used for antiviral immunotherapy in clinic. Therefore, identification of the regulators of IFN-I antiviral activity is important for developing novel targets for IFN-based antiviral therapy. Monocyte chemoattractant protein 1-induced protein 1 (MCPIP1) is critical for cellular inflammatory responses. However, the roles of MCPIP1 in interferons (IFNs)-mediated antiviral immunity are unexplored. In this study, we demonstrate for the first time that MCPIP1 is an important positive regulator of IFNs antiviral activity...
March 12, 2018: Biochemical and Biophysical Research Communications
Alexandre Karras
Cryoglobulins are immunoglobulins that undergo reversible precipitation at low temperatures. They can induce systemic vasculitis, characterized by purpuric cutaneous lesions, arthritis, peripheral neuropathy, hypocomplementemia and glomerular disease. Renal pathology reveals membranoproliferative glomerulonephritis, with particularly intense mesangial cell proliferation and infiltration by macrophages, associated with intracapillary thrombi. This renal disease presents as a nephritic syndrome, with heavy proteinuria, haematuria severe hypertension and rapidly progressive kidney failure that can lead to end-stage renal disease...
March 12, 2018: Néphrologie & Thérapeutique
Richard Lindqvist, Chaitanya Kurhade, Jonathan D Gilthorpe, Anna K Överby
BACKGROUND: Flaviviruses are a group of diverse and emerging arboviruses and an immense global health problem. A number of flaviviruses are neurotropic, causing severe encephalitis and even death. Type I interferons (IFNs) are the first line of defense of the innate immune system against flavivirus infection. IFNs elicit the concerted action of numerous interferon-stimulated genes (ISGs) to restrict both virus infection and replication. Viperin (virus-inhibitory protein, endoplasmic reticulum-associated, IFN-inducible) is an ISG with broad-spectrum antiviral activity against multiple flaviviruses in vitro...
March 15, 2018: Journal of Neuroinflammation
Soon Young Ko, Won Hyeok Choe
The advent of novel, direct-acting antiviral (DAA) regimens for hepatitis C viral (HCV) infection has revolutionized its treatment by producing a sustained virologic response of more than 95% with few side effects and no comorbidities in the general population. Until recently, ideal DAA regimens have not been available to patients with severe renal impairment and end-stage renal disease because there are limited data on the pharmacokinetics, safety, and efficacy of treatment in this unique population. In a hemodialysis context, identifying patients in need of treatment and preventing HCV transmission may also be a matter of concern...
March 16, 2018: Clinical and Molecular Hepatology
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