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https://www.readbyqxmd.com/read/28650973/interferon-signaling-in-peromyscus-leucopus-confers-a-potent-and-specific-restriction-to-vector-borne-flaviviruses
#1
Adaeze O Izuogu, Kristin L McNally, Stephen E Harris, Brian H Youseff, John B Presloid, Christopher Burlak, Jason Munshi-South, Sonja M Best, R Travis Taylor
Tick-borne flaviviruses (TBFVs), including Powassan virus and tick-borne encephalitis virus cause encephalitis or hemorrhagic fevers in humans with case-fatality rates ranging from 1-30%. Despite severe disease in humans, TBFV infection of natural rodent hosts has little noticeable effect. Currently, the basis for resistance to disease is not known. We hypothesize that the coevolution of flaviviruses with their respective hosts has shaped the evolution of potent antiviral factors that suppress virus replication and protect the host from lethal infection...
2017: PloS One
https://www.readbyqxmd.com/read/28643404/occurrence-of-late-relapse-of-hepatitis-c-virus-confirmed-by-molecular-analysis-after-sustained-virological-response-to-interferon-ribavirin-based-therapy
#2
Kazuhiko Hayashi, Masatoshi Ishigami, Satoshi Yasuda, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Tetsuya Ishikawa, Yoshiki Hirooka, Hidemi Goto
BACKGROUND AND AIM: The optimal duration of follow-up for patients who achieve sustained virological responses (SVR) has become an important issue. Reports on long-term follow-up of SVR have demonstrated that 99% of patients maintained SVR. However, the limitations of a majority of studies include small patient numbers, short study periods, and lack of molecular analysis of hepatitis C virus (HCV) genome. The present study sought to evaluate the late relapse rate in long-term follow-up of patients who achieved SVR, with molecular analysis of HCV...
June 22, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28634750/t135i-substitution-in-the-nonstructural-protein-2c-enhances-foot-and-mouth-disease-virus-replication
#3
Tiangang Yuan, Haiwei Wang, Chen Li, Decheng Yang, Guohui Zhou, Li Yu
The foot-and-mouth disease virus (FMDV) nonstructural protein 3A plays an important role in viral replication, virulence, and host range. It has been shown that deletions of 10 or 19-20 amino acids in the C-terminal half of 3A attenuate serotype O and C FMDVs, which replicate poorly in bovine cells but normally in porcine-derived cells, and the C-terminal half of 3A is not essential for serotype Asia1 FMDV replication in BHK-21 cells. In this study, we constructed a 3A deletion FMDV mutant based on a serotype O FMDV, the wild-type virus O/YS/CHA/05, with a 60-amino acid deletion in the 3A protein sequence, between residues 84 and 143...
June 20, 2017: Virus Genes
https://www.readbyqxmd.com/read/28631603/a-single-point-mutation-in-tomato-spotted-wilt-virus-nss-protein-is-sufficient-to-overcome-tsw-gene-mediated-resistance-in-pepper
#4
Asztéria Almási, Katalin Nemes, Zsófia Csömör, István Tóbiás, László Palkovics, Katalin Salánki
The nonstructural protein (NSs) of Tomato spotted wilt virus (TSWV) was previously identified as an avirulence determinant for Tsw-based resistance on pepper. The NSs of wild-type (WT) and resistance-breaking (RB) TSWV strains isolated in Hungary had only two amino acid substitutions (104, 461). We have analysed the ability of the NSs and their point mutant variants to trigger Tsw-mediated hypersensitive responses and RNA silencing suppressor (RSS) activity in patch assays. We identified a single amino acid change at position 104 (T-A) that was responsible for the necrosis induction or loss, while a significant difference was not detected in the RSS activity of the two parental strains...
June 20, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28621007/effectiveness-of-a-fixed-combination-formula-of-ombitasvir-paritaprevir-ritonavir-for-hepatitis-c-virus-infection-in-patients-on-maintenance-haemodialysis
#5
Norihiko Morisawa, Yohei Koshima, Satoru Kuriyama, Momoko Matsuyama, Naomi Hayashi, Jun-Ichi Satoh, Morimasa Amemiya, Takashi Yokoo
A fixed-dose formula that combines Ombitasvir (OBV), Paritaprevir (PTV) and Ritonavir (RTV) has been launched into the field of anti-HCV therapy in Japan for patients infected with HCV genotypes 1 and 2 in 2015. However, little is yet known as to the efficacy and safety of this novel therapy in patients on maintenance haemodialysis (HD). The present report describes a preliminary experience in 10 patients (five males and five females) who underwent maintenance HD. All of them had HCV genotype 1b, without having the resistance-associated variants at Y93 or L31 in the nonstructural proteins 5A (NS5A) region...
July 2017: Nephrology
https://www.readbyqxmd.com/read/28619163/frequent-occurrence-of-nonprimate-hepacivirus-infections-in-thoroughbred-breeding-horses-a-cross-sectional-study-for-the-occurrence-of-infections-and-potential-risk-factors
#6
Claudia Reichert, Amely Campe, Stephanie Walter, Stephanie Pfaender, Kathrin Welsch, Inga Ruddat, Harald Sieme, Karsten Feige, Eike Steinmann, Jessika M V Cavalleri
Recently, several new hepaciviruses have been identified of which the nonprimate hepacivirus (NPHV) - the closest relative to hepatitis C virus (HCV) discovered to date - is highly prevalent in horses. However, potential risk factors for the transmission of NPHV among horses remain still unknown. Therefore, the objective of this study was to investigate the occurrence of NPHV infections in Thoroughbreds in northern and western Germany and to identify potential risk factors associated with NPHV infections. Using a cross-sectional study design, a total of 733 serum samples from Thoroughbred broodmares and stallions from northern and western Germany were analyzed for the presence of anti-NPHV nonstructural protein 3 (NS3) antibodies and NPHV RNA using the luciferase immunoprecipitation system (LIPS) and a quantitative real-time PCR, respectively...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28597195/identification-of-epitopes-on-nonstructural-protein-7-of-porcine-reproductive-and-respiratory-syndrome-virus-recognized-by-monoclonal-antibodies-using-phage-display-technology
#7
Heng Wang, Rongchang Liu, Weidong Zhang, Lingshuang Sun, Zhangyong Ning, Fangxiao Ji, Jin Cui, Guihong Zhang
Nonstructural protein 7 (nsp7) of porcine reproductive and respiratory syndrome virus (PRRSV) is considered to be a suitable reagent for the development of serological diagnostic assays. It can be expressed as a soluble recombinant protein in Escherichia coli, and its antibody response may continue up to 202 days post-infection. Furthermore, the region encoded by nsp7 is highly homologous among various strains within the genotype, and the results of nsp7-based enzyme-linked immunosorbent assay (ELISA) showed high agreement with previous Idexx ELISA results...
June 8, 2017: Virus Genes
https://www.readbyqxmd.com/read/28592628/chemiluminescence-immunoassay-for-the-detection-of-antibodies-against-the-2c-and-3abc-nonstructural-proteins-induced-by-infecting-pigs-with-the-foot-and-mouth-disease-virus
#8
Zezhong Liu, Junjun Shao, Furong Zhao, Guangqing Zhou, Shandian Gao, Wei Liu, Jianliang Lv, Xiumei Li, Yangfan Li, Huiyun Chang, Yongguang Zhang
The potential diagnostic value of chemiluminescence immunoassays (CLIAs) has been accepted in recent years, although its use for foot-and-mouth disease (FMD) diagnostics has not been reported. Full-length 3ABC and 2C proteins were expressed in bacteria and purified by affinity chromatography to develop a rapid and accurate approach to distinguish pigs infected with foot-and-mouth disease virus (FMDV) from vaccinated pigs (DIVA). The recombinant proteins were then used as antigens to develop two CLIAs for the detection of antibodies against nonstructural viral proteins...
June 7, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28580734/sars-unique-fold-in-the-rousettus-bat-coronavirus-hku9
#9
Robert G Hammond, Xuan Tan, Margaret A Johnson
The coronavirus nonstructural protein 3 (nsp3) is a multifunctional protein that comprises multiple structural domains. This protein assists viral polyprotein cleavage, host immune interference, and may play other roles in genome replication or transcription. Here, we report the solution NMR structure of a protein from the "SARS-unique region" of the bat coronavirus HKU9. The protein contains a frataxin fold or double-wing motif, which is an α + β fold that is associated with protein/protein interactions, DNA binding, and metal ion binding...
June 5, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28572406/how-an-alloreactive-t-cell-receptor-achieves-peptide-and-mhc-specificity
#10
Yuan Wang, Nishant K Singh, Timothy T Spear, Lance M Hellman, Kurt H Piepenbrink, Rachel H McMahan, Hugo R Rosen, Craig W Vander Kooi, Michael I Nishimura, Brian M Baker
T-cell receptor (TCR) allorecognition is often presumed to be relatively nonspecific, attributable to either a TCR focus on exposed major histocompatibility complex (MHC) polymorphisms or the degenerate recognition of allopeptides. However, paradoxically, alloreactivity can proceed with high peptide and MHC specificity. Although the underlying mechanisms remain unclear, the existence of highly specific alloreactive TCRs has led to their use as immunotherapeutics that can circumvent central tolerance and limit graft-versus-host disease...
June 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28570623/genetic-diversity-of-hepatitis-c-virus-in-ethiopia
#11
Gadissa Bedada Hundie, V Stalin Raj, Daniel GebreMichael, Suzan D Pas, Bart L Haagmans
Hepatitis C virus (HCV) is genetically highly divergent and classified in seven major genotypes and approximately hundred subtypes. These genotypes/subtypes have different geographic distribution and response to antiviral therapy. In Ethiopia, however, little is known about their molecular epidemiology and genetic diversity. The aim of this study was to investigate the distribution and genetic diversity of HCV genotypes/subtypes in Ethiopia, using 49 HCV RNA positive samples. HCV genotypes and subtypes were determined based on the sequences of the core and the nonstructural protein 5B (NS5B) genomic regions...
2017: PloS One
https://www.readbyqxmd.com/read/28566381/hepatitis-c-virus-subverts-human-choline-kinase-%C3%AE-to-bridge-pi4kiii%C3%AE-and-ns5a-and-upregulates-pi4kiii%C3%AE-activation-thereby-promoting-the-translocation-of-the-ternary-complex-to-the-er-for-viral-replication
#12
Mun-Teng Wong, Steve S Chen
In this study, we elucidated the mechanism by which human choline kinase-α (hCKα) interacts with nonstructural protein (NS)5A and phosphatidylinositol-4-kinase (PI4K)IIIα, the lipid kinase crucial for maintaining the integrity of virus-induced membranous webs, and modulates hepatitis C virus (HCV) replication. hCKα activity positively modulated PI-4-phosphate (PI4P) levels in HCV-expressing cells, and hCKα-mediated PI4P accumulation was abolished by AL-9, a PI4KIIIα-specific inhibitor. hCKα colocalized with NS5A and PI4KIIIα or PI4P, NS5A expression increased hCKα and PI4KIIIα colocalization, and hCKα formed a ternary complex with PI4KIIIα and NS5A, supporting the functional interplay of hCKα with PI4KIIIα and NS5A...
May 31, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28560477/daclatasvir-and-asunaprevir-in-hemodialysis-patients-with-hepatitis-c-virus-infection-a-nationwide-retrospective-study-in-japan
#13
Goki Suda, Norihiro Furusyo, Hidenori Toyoda, Yoshiiku Kawakami, Hiroki Ikeda, Michihiro Suzuki, Keiko Arataki, Nami Mori, Keiji Tsuji, Yoshio Katamura, Koichi Takaguchi, Toru Ishikawa, Kunihiko Tsuji, Noritomo Shimada, Atsushi Hiraoka, Sho Yamsaki, Masato Nakai, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Mineo Kudo, Atsushi Nagasaka, Ken Furuya, Yoshiya Yamamoto, Kanji Kato, Yoshiyuki Ueno, Etsuko Iio, Yasuhito Tanaka, Masayuki Kurosaki, Takashi Kumada, Kazuaki Chayama, Naoya Sakamoto
BACKGROUND: Hepatitis C virus (HCV) infection is common in hemodialysis patients and worsens their prognosis, while antiviral therapy options are limited. Recently, clinical trial and real-world, small-scale studies have reported excellent responses to direct-acting antivirals in patients with advanced chronic kidney diseases. However, real-world, large-scale data were lacking. This large multicenter analysis included HCV-infected hemodialysis patients receiving combination therapy with a nonstructural protein 5A (NS5A) inhibitor, daclatasvir (DCV), and a protease inhibitor, asunaprevir (ASV)...
May 30, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28545480/effects-of-hepatitis-c-virus-core-protein-and-nonstructural-protein-4b-on-the-wnt-%C3%AE-catenin-pathway
#14
Xiao-Hua Jiang, Yu-Tao Xie, Ya-Ping Cai, Jing Ren, Tao Ma
BACKGROUND: Hepatitis C virus (HCV) core protein and nonstructural protein 4B (NS4B) are potentially oncogenic. Aberrant activation of the Wnt/β-catenin signaling pathway is closely associated with hepatocarcinogenesis. We investigated the effects of HCV type 1b core protein and NS4B on Wnt/β-catenin signaling in various liver cells, and explored the molecular mechanism underlying HCV-related hepatocarcinogenesis. RESULTS: Compared with the empty vector control, HCV core protein and NS4B demonstrated the following characteristics in the Huh7 cells: significantly enhanced β-catenin/Tcf-dependent transcriptional activity (F = 40...
May 25, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28539454/ebola-virus-delta-peptide-is-a-viroporin
#15
Jing He, Lilia I Melnik, Alexander Komin, Gregory Wiedman, Taylor Fuselier, Cameron F Morris, Charles G Starr, Peter C Searson, William R Gallaher, Kalina Hristova, Robert F Garry, William C Wimley
The Ebola virus (EBOV) genome encodes for a partly conserved, 40-residue, nonstructural polypeptide, called the delta peptide, which is produced in abundance during Ebola virus disease. The function of the delta peptide is unknown, but sequence analysis has suggested that delta peptide could be a viroporin, belonging to a diverse family of membrane-permeabilizing small polypeptides involved in replication and pathogenesis of numerous viruses. Full length and conserved C-terminal delta peptide fragments permeabilize the plasma membranes of nucleated cells of rodent, dog, monkey and human origin, increase ion permeability across confluent cell monolayers and permeabilize synthetic lipid bilayers...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28535337/overall-structural-model-of-ns5a-protein-from-hepatitis-c-virus-and-modulation-by-mutations-confering-resistance-of-virus-replication-to-cyclosporin-a
#16
Aurelie Badillo, Véronique Receveur-Brechot, Stéphane Sarrazin, François-Xavier Cantrelle, Frédéric Delolme, Marie-Laure Fogeron, Jennifer Molle, Roland Montserret, Anja Bockmann, Ralf Bartenschlager, Volker Lohmann, Guy Lippens, Sylvie Ricard-Blum, Xavier Hanoulle, François Penin
Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a RNA-binding phosphoprotein composed of a N-terminal membrane anchor (AH), a structured domain 1 (D1), and two intrinsically disordered domains (D2 and D3). The knowledge of the functional architecture of this multifunctional protein remains limited. We report here that NS5A-D1D2D3 produced in a wheat germ cell-free system is obtained under a highly phosphorylated state. Its NMR analysis revealed that these phosphorylations do not change the disordered nature of D2 and D3 domains but increase the number of conformers due to partial phosphorylations...
June 7, 2017: Biochemistry
https://www.readbyqxmd.com/read/28529975/phylogenetic-analyses-suggest-that-factors-other-than-the-capsid-protein-play-a-role-in-the-epidemic-potential-of-gii-2-norovirus
#17
Kentaro Tohma, Cara J Lepore, Lauren A Ford-Siltz, Gabriel I Parra
Norovirus is the leading cause of acute gastroenteritis worldwide. For over two decades, a single genotype (GII.4) has been responsible for most norovirus-associated cases. However, during the winter of 2014 to 2015, the GII.4 strains were displaced by a rarely detected genotype (GII.17) in several countries of the Asian continent. Moreover, during the winter of 2016 to 2017, the GII.2 strain reemerged as predominant in different countries worldwide. This reemerging GII.2 strain is a recombinant virus that presents a GII...
May 2017: MSphere
https://www.readbyqxmd.com/read/28527257/-polyclonal-antibodies-against-recombinant-dengue-virus-ns3-protein
#18
Liliana Morales, Myriam L Velandia, María Angélica Calderon, Jaime E Castellanos, Jacqueline Chaparro-Olaya
INTRODUCTION: Dengue is a disease caused by one of four serotypes of the dengue virus (DENV) and is endemic in approximately 130 countries. The incidence of dengue has increased dramatically in recent decades, as well as the frequency and magnitude of outbreaks. Despite all efforts, there are no prophylactic or therapeutic treatments for the disease. Accordingly, research on the processes governing the DENV infection cycle is essential to develop vaccines or antiviral therapies. One of themost attractive DENV molecules to investigate is nonstructural protein 3 (NS3), which is essential for viral replication and a major immune target for infection...
January 24, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28518476/adult-onset-chronic-cyclic-thrombocytopenia-in-a-rhesus-macaque-macaca-mulatta-after-dengue-virus-vaccination-and-viral-challenge
#19
Galit H Frydman, Kelly A Metcalf Pate, Robert P Marini, Armelle M de Laforcade, Irene Bosch, Vasudevan Bakthavatchalu, Sureshkumar Muthupalani, Alton G Swennes, Claire E Lyons, Ronald G Tompkins, James G Fox
An 8-year-old, male Rhesus macaque (Macaca mulatta), previously used for dengue virus (DENV) vaccine research with viral challenge, was presented with adult-onset, chronic, cyclic thrombocytopenia. Platelet number, morphology, and function were evaluated by automated hematology, peripheral blood smears, electron microscopy, flow cytometry, and impedance aggregometry. Bone marrow was evaluated by cytology. Both serum anti-dengue nonstructural protein 1 (NS1) antibodies and anti-platelet antibodies were detected by ELISA...
June 2017: Veterinary Clinical Pathology
https://www.readbyqxmd.com/read/28514196/interactions-between-ns1-of-influenza-a-viruses-and-interferon-%C3%AE-%C3%AE-determinants-for-vaccine-development
#20
Ben X Wang, Eleanor N Fish
Influenza A viruses (IAVs) cause mild to severe infections in humans with considerable socioeconomic and global health consequences. The host interferon (IFN)-α/β response, critical as the first line of defense against foreign pathogens, is induced upon detection of IAV genomic RNA in infected cells by host innate pattern recognition receptors. IFN-α/β production and subsequent activation of cell signaling result in the expression of antiviral IFN-stimulated genes whose products target various stages of the IAV life cycle to inhibit viral replication and the spread of infection and establish an antiviral state...
May 17, 2017: Journal of Interferon & Cytokine Research
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