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https://www.readbyqxmd.com/read/28814517/zinc-salts-block-hepatitis-e-virus-replication-by-inhibiting-the-activity-of-viral-rna-dependent-rna-polymerase
#1
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/28814513/escape-of-tick-borne-flavivirus-from-2-c-methylated-nucleoside-antivirals-is-mediated-by-a-single-conservative-mutation-in-ns5-that-has-a-dramatic-effect-on-viral-fitness
#2
Ludek Eyer, Hirofumi Kondo, Darina Zouharova, Minato Hirano, James J Valdés, Memi Muto, Tomas Kastl, Shintaro Kobayashi, Jan Haviernik, Manabu Igarashi, Hiroaki Kariwa, Marketa Vaculovicova, Jiri Cerny, Rene Kizek, Andrea Kröger, Stefan Lienenklaus, Milan Dejmek, Radim Nencka, Martin Palus, Jiri Salat, Erik De Clercq, Kentaro Yoshii, Daniel Ruzek
Tick-borne encephalitis virus (TBEV) causes a severe and potentially fatal neuroinfection in humans. Despite its high medical relevance, no specific antiviral therapy is currently available. Here we demonstrate that treatment with a nucleoside analog, 7-deaza-2' -C-methyladenosine (7-deaza-2' -CMA), substantially improved disease outcome, increased survival, and reduced signs of neuroinfection and viral titers in the brains of mice infected with a lethal dose of TBEV. To investigate the mechanism of action of 7-deaza-2' -CMA, two drug-resistant TBEV clones were generated and characterized...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28807916/inhibition-of-calcineurin-or-impdh-exerts-moderate-to-potent-antiviral-activity-against-norovirus-replication
#3
Wen Dang, Yuebang Yin, Yijin Wang, Wenshi Wang, Junhong Su, Dave Sprengers, Luc J W van der Laan, Krzysztof Felczak, Krzysztof W Pankiewicz, Kyeong-Ok Chang, Marion P G Koopmans, Herold J Metselaar, Maikel P Peppelenbosch, Qiuwei Pan
Norovirus is a major cause of acute gastroenteritis worldwide and has emerged as an important issue of chronic infection in transplantation patients. Since no approved antiviral is available, we evaluated the effects of different immunosuppressants and ribavirin on norovirus and explored their mechanism-of-actions by using a human norovirus (HuNV) replicon-harboring model and a surrogate murine norovirus (MNV) infectious model. Roles of corresponding drug targets were investigated by gain- or loss-of-function approaches...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28802584/molecular-characterization-of-the-pa3j1-plasmid-from-the-psychrotolerant-antarctic-bacterium-pseudomonas-sp-ant_j3
#4
Krzysztof Romaniuk, Tomasz Krucon, Przemyslaw Decewicz, Adrian Gorecki, Lukasz Dziewit
The knowledge on plasmids of cold-active bacteria is highly limited. In this study, the molecular characterization of the pA3J1 plasmid of Antarctic psychrotolerant bacterium Pseudomonas sp. ANT_J3 was performed. Within this plasmid, thirteen putative open reading frames were identified. Nine of them encoded proteins involved in replication, partitioning, postsegregational elimination of plasmid-less cells (via a toxin-antitoxin system activity), multimer resolution and mobilization by conjugal transfer. These genes constitute the plasmid backbone...
August 9, 2017: Plasmid
https://www.readbyqxmd.com/read/28802274/horizontal-dissemination-of-antimicrobial-resistance-determinants-in-multiple-salmonella-serotypes-following-isolation-from-the-environment-of-commercial-swine-operations-after-manure-application
#5
Suchawan Pornsukarom, Siddhartha Thakur
The aim of this study was to characterize the plasmids carrying antimicrobial resistance (AMR) determinants in multiple Salmonella serotypes recovered from the commercial swine farms environment after manure application on land. Manure and soil samples were collected on day0 before and after manure application on six farms in North Carolina and sequential soil samples were recollected on day7, 14, and 21 from the same plots. All environmental samples were processed for Salmonella and their plasmid contents were further characterized...
August 11, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28800133/adaptive-evolution-of-rhizobial-symbiotic-compatibility-mediated-by-co-evolved-insertion-sequences
#6
Ran Zhao, Li Xue Liu, Yun Zeng Zhang, Jian Jiao, Wen Jing Cui, Biliang Zhang, Xiao Lin Wang, Meng Lin Li, Yi Chen, Zhu Qing Xiong, Wen Xin Chen, Chang Fu Tian
Mutualism between bacteria and eukaryotes has essential roles in the history of life, but the evolution of their compatibility is poorly understood. Here we show that different Sinorhizobium strains can form either nitrogen-fixing nodules or uninfected pseudonodules on certain cultivated soybeans, while being all effective microsymbionts of some wild soybeans. However, a few well-infected nodules can be found on a commercial soybean using inocula containing a mixed pool of Tn5 insertion mutants derived from an incompatible strain...
August 11, 2017: ISME Journal
https://www.readbyqxmd.com/read/28798737/complete-genome-analysis-of-thermus-parvatiensis-and-comparative-genomics-of-thermus-spp-provide-insights-into-genetic-variability-and-evolution-of-natural-competence-as-strategic-survival-attributes
#7
Charu Tripathi, Harshita Mishra, Himani Khurana, Vatsala Dwivedi, Komal Kamra, Ram K Negi, Rup Lal
Thermophilic environments represent an interesting niche. Among thermophiles, the genus Thermus is among the most studied genera. In this study, we have sequenced the genome of Thermus parvatiensis strain RL, a thermophile isolated from Himalayan hot water springs (temperature >96°C) using PacBio RSII SMRT technique. The small genome (2.01 Mbp) comprises a chromosome (1.87 Mbp) and a plasmid (143 Kbp), designated in this study as pTP143. Annotation revealed a high number of repair genes, a squeezed genome but containing highly plastic plasmid with transposases, integrases, mobile elements and hypothetical proteins (44%)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28795221/development-of-the-first-gene-expression-system-for-salinicoccus-strains-with-potential-application-in-bioremediation-of-hypersaline-wastewaters
#8
Dahe Zhao, Haibo Yang, Junyu Chen, Feiyue Cheng, Sumit Kumar, Jing Han, Ming Li, Jian Zhou, Hua Xiang
Salinicoccus salsiraiae IM408 (=CGMCC13032) is a novel halophilic bacterium that we isolated from the saline soil of Da Gang Oilfield. It tolerates 60 g/l sodium chloride and up to 123 g/l (1.5 M) sodium acetate and has shown a potential application in bioremediation of wastewater with high salt and high chemical oxygen demand (COD). Two plasmids, pS408-1 and pS408-2, were identified in S. salsiraiae IM408, and the sequences and copy numbers of the plasmids were determined. Based on these plasmids, two shuttle vectors containing a replicon for Escherichia coli, ampicillin, and chloramphenicol resistance genes, as well as the replicon from pS408-1 or pS408-2, were constructed and named as pTCS101 and pTCS201, respectively...
August 9, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28794225/the-divided-bacterial-genome-structure-function-and-evolution
#9
REVIEW
George C diCenzo, Turlough M Finan
Approximately 10% of bacterial genomes are split between two or more large DNA fragments, a genome architecture referred to as a multipartite genome. This multipartite organization is found in many important organisms, including plant symbionts, such as the nitrogen-fixing rhizobia, and plant, animal, and human pathogens, including the genera Brucella, Vibrio, and Burkholderia. The availability of many complete bacterial genome sequences means that we can now examine on a broad scale the characteristics of the different types of DNA molecules in a genome...
September 2017: Microbiology and Molecular Biology Reviews: MMBR
https://www.readbyqxmd.com/read/28794019/development-of-virus-like-particle-vaccine-and-reporter-assay-for-zika-virus
#10
Himanshu Garg, Melina Sedano, Gabrielle Plata, Erin B Punke, Anjali Joshi
Recent worldwide outbreaks of Zika virus (ZIKV) infection and the lack of an approved vaccine raises serious concerns regarding preparedness to combat this emerging virus. We used a Virus Like Particle (VLP) based approach to develop a vaccine and a microneutralization assay against ZIKV. Synthetic C-prM-E (Capsid-preMembrane-Envelope) gene construct of ZIKV was used to generate Reporter Virus Particles (RVPs) that package GFP reporter expressing WNV replicon. The assay was adapted to 96 well format, similar to the Plaque Reduction Neutralization Test (PRNT) and showed high reproducibility with specific detection of ZIKV neutralizing antibodies...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28780423/cinnamic-acid-derivatives-inhibit-hepatitis-c-virus-replication-via-the-induction-of-oxidative-stress
#11
Ryota Amano, Atsuya Yamashita, Hirotake Kasai, Tomoka Hori, Sayoko Miyasato, Setsu Saito, Hiromasa Yokoe, Kazunori Takahashi, Tomohisa Tanaka, Teruhime Otoguro, Shinya Maekawa, Nobuyuki Enomoto, Masayoshi Tsubuki, Kohji Moriishi
Several cinnamic acid derivatives have been reported to exhibit antiviral activity. In this study, we prepared 17 synthetic cinnamic acid derivatives and screened them to identify an effective antiviral compound against hepatitis C virus (HCV). Compound 6, one of two hit compounds, suppressed the viral replications of genotypes 1b, 2a, 3a, and 4a with EC50 values of 1.5-8.1 μM and SI values of 16.2-94.2. The effect of compound 6 on the phosphorylation of Tyr(705) in signal transducer and activator of transcription 3 (STAT3) was investigated because a cinnamic acid derivative AG490 was reported to suppress HCV replication and the activity of Janus kinase (JAK) 2...
August 2, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28776045/whole-genome-sequencing-of-human-clinical-klebsiella-pneumoniae-isolates-reveals-misidentification-and-misunderstandings-of-klebsiella-pneumoniae-klebsiella-variicola-and-klebsiella-quasipneumoniae
#12
S Wesley Long, Sarah E Linson, Matthew Ojeda Saavedra, Concepcion Cantu, James J Davis, Thomas Brettin, Randall J Olsen
Klebsiella pneumoniae is a major threat to public health, causing significant morbidity and mortality worldwide. The emergence of highly drug-resistant strains is particularly concerning. There has been a recognition and division of Klebsiella pneumoniae into three distinct phylogenetic groups: Klebsiella pneumoniae, Klebsiella variicola, and Klebsiella quasipneumoniae. K. variicola and K. quasipneumoniae have often been described as opportunistic pathogens that have less virulence in humans than K. pneumoniae does...
July 2017: MSphere
https://www.readbyqxmd.com/read/28772350/claudin-1-mir-122-and-apolipoprotein-e-transduction-improves-the-permissivity-of-snu-182-snu-398-and-snu-449-hepatoma-cells-to-hepatitis-c-virus
#13
Carole Fournier, Thomas Walter Hoffmann, Virginie Morel, Véronique Descamps, Jean Dubuisson, Etienne Brochot, Catherine Francois, Gilles Duverlie, Sandrine Castelain, Francois Helle
Hepatitis C virus (HCV) is a human hepatotropic virus but many hepatoma cell lines are not permissive to this virus. In a previous study, we observed that SNU-182, SNU-398 and SNU-449 hepatoma cell lines were non-permissive to HCV. In order to understand the non-permissivity, we evaluated the ability of each cell line to support the different steps of HCV life cycle (entry, replication and production of infectious particles). Using retroviral pseudoparticles pseudotyped with HCV envelope proteins and recombinant HCV produced in cell culture, we observed that low level or absence of claudin-1 expression limited the viral entry process in SNU-182 and SNU-398 cells, respectively...
August 3, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28769910/plasmid-transfer-in-the-ocean-a-case-study-from-the-roseobacter-group
#14
Jörn Petersen, Irene Wagner-Döbler
Plasmid mediated horizontal gene transfer (HGT) has been speculated to be one of the prime mechanisms for the adaptation of roseobacters (Rhodobacteraceae) to their ecological niches in the marine habitat. Their plasmids contain ecologically crucial functional modules of up to ∼40-kb in size, e.g., for aerobic anoxygenic photosynthesis, flagellar formation and the biosynthesis of the antibiotic tropodithietic acid. Furthermore, the widely present type four secretion system (T4SS) of roseobacters has been shown to mediate conjugation across genus barriers, albeit in the laboratory...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28764701/a-versatile-one-step-crispr-cas9-based-approach-to-plasmid-curing
#15
Ida Lauritsen, Andreas Porse, Morten O A Sommer, Morten H H Nørholm
BACKGROUND: Plasmids are widely used and essential tools in molecular biology. However, plasmids often impose a metabolic burden and are only temporarily useful for genetic engineering, bio-sensing and characterization purposes. While numerous techniques for genetic manipulation exist, a universal tool enabling rapid removal of plasmids from bacterial cells is lacking. RESULTS: Based on replicon abundance and sequence conservation analysis, we show that the vast majority of bacterial cloning and expression vectors share sequence similarities that allow for broad CRISPR-Cas9 targeting...
August 2, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28751105/permissiveness-of-human-hepatocellular-carcinoma-cell-lines-for-hepatitis-c-virus-entry-and-replication
#16
Mairene Coto-Llerena, George Koutsoudakis, Loreto Boix, Juan Manuel López-Oliva, Noelia Caro-Pérez, Carlos Fernández-Carrillo, Patricia González, Pablo Gastaminza, Jordi Bruix, Xavier Forns, Sofía Pérez-Del-Pulgar
Hepatitis C virus (HCV) is a globally prevalent pathogen and is associated with high death rates and morbidity. Since its discovery in 1989, HCV research has been impeded by the lack of a robust infectious cell culture system and thus in vitro studies on diverse genetic backgrounds are hampered because of the limited number of hepatoma cell lines which are able to support different aspects of the HCV life cycle. In the current study, we sought to expand the limited number of permissive cells capable of supporting the diverse phases of the HCV life cycle...
July 24, 2017: Virus Research
https://www.readbyqxmd.com/read/28747506/hcv-induces-the-localization-of-lipid-rafts-to-autophagosomes-for-its-rna-replication
#17
Ja Yeon Kim, Linya Wang, Jiyoung Lee, Jing-Hsiung James Ou
Autophagy plays important roles in maintaining cellular homeostasis. It uses double- or multiple- membrane vesicles termed autophagosomes to remove protein aggregates and damaged organelles from the cytoplasm for recycling. Hepatitis C virus (HCV) has been shown to induce autophagy to enhance its own replication. Here we describe a procedure that combines membrane flotation and affinity chromatography for the purification of autophagosomes from cells that harbor a HCV subgenomic RNA replicon. The purified autophagosomes had double- or multiple- membrane structures with a diameter ranging from 200 nm to 600 nm...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28741898/development-of-a-new-structural-class-of-broadly-acting-hcv-non-nucleoside-inhibitors-leading-to-the-discovery-of-mk-8876
#18
Casey C McComas, Anandan Palani, Wei Chang, M Katharine Holloway, Charles A Lesburg, Peng Li, Nigel Liverton, Peter T Meinke, David B Olsen, Xuanjia Peng, Richard M Soll, Ajay Ummat, Jie Wu, Jin Wu, Nicolas Zorn, Steven W Ludmerer
Studies directed at developing a broadly acting non-nucleoside inhibitor of HCV NS5B led to the discovery of a novel structural class of 5-aryl benzofurans that simultaneously interact with both the palm I and palm II binding regions. An initial candidate was potent in vitro against HCV GT1a and GT1b replicons, and induced multi-log reductions in HCV viral load when orally dosed to chronic GT1 infected chimpanzees. However, in vitro potency losses against clinically relevant GT1a variants prompted a further effort to develop compounds with sustained potency across a broader array of HCV genotypes and mutants...
July 25, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28740748/a-highly-pathogenic-porcine-reproductive-and-respiratory-syndrome-virus-candidate-vaccine-based-on-japanese-encephalitis-virus-replicon-system
#19
Pingsheng Hu, Xiaoming Chen, Lihong Huang, Shukai Liu, Fuyu Zang, Jinchao Xing, Youyue Zhang, Jiaqi Liang, Guihong Zhang, Ming Liao, Wenbao Qi
In the swine industry, porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease which causes heavy economic losses worldwide. Effective prevention and disease control is an important issue. In this study, we described the construction of a Japanese encephalitis virus (JEV) DNA-based replicon with a cytomegalovirus (CMV) promoter based on the genome of Japanese encephalitis live vaccine virus SA14-14-2, which is capable of offering a potentially novel way to develop and produce vaccines against a major pathogen of global health...
2017: PeerJ
https://www.readbyqxmd.com/read/28738245/two-amino-acids-change-in-the-nsp4-of-sars-coronavirus-abolishes-viral-replication
#20
Yusuke Sakai, Kengo Kawachi, Yutaka Terada, Hiroko Omori, Yoshiharu Matsuura, Wataru Kamitani
Infection with coronavirus rearranges the host cell membrane to assemble a replication/transcription complex in which replication of the viral genome and transcription of viral mRNA occur. Although coexistence of nsp3 and nsp4 is known to cause membrane rearrangement, the mechanisms underlying the interaction of these two proteins remain unclear. We demonstrated that binding of nsp4 with nsp3 is essential for membrane rearrangement and identified amino acid residues in nsp4 responsible for the interaction with nsp3...
July 21, 2017: Virology
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