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https://www.readbyqxmd.com/read/27922182/retinoid-derivative-tp80-exhibits-anti-hepatitis-c-virus-activity-through-restoration-of-gi-gpx-expression
#1
Nguyen Bao Ngoc, Yukiko Okuno, Masahiko Ajiro, Kei Iida, Masatsugu Denawa, Makoto Yamamoto, Naoya Sakamoto, Hiroyuki Kagechika, Masatoshi Hagiwara
Hepatitis C virus (HCV) is a positive-sense single-stranded RNA virus with an estimated infection in ∼180 million people worldwide, and its chronic infection leads to development of cirrhosis and hepatocellular carcinoma. Although recent development of direct acting antiviral (DAA) compounds improved anti-HCV regimens, alternative therapeutic compounds are still demanded due to an expected emergence of escape mutants for those DAAs. In order to identify novel anti-HCV agents, we conducted chemical library screening for 2,086 compounds using HCV Rep-Feo reporter replicon in Huh7 hepatoma cells...
December 6, 2016: Journal of Medical Virology
https://www.readbyqxmd.com/read/27919902/genetic-environment-of-the-blakpc-2-gene-in-klebsiella-pneumoniae-isolate-which-may-have-been-imported-to-russia-from-southeast-asia
#2
Vladimir Ageevets, Julia Sopova, Irina Lazareva, Maya Malakhova, Elena Ilina, Elena Kostryukova, Vladislav Babenko, Alessandra Carattoli, Yuri Lobzin, Alexander Uskov, Sergey Sidorenko
The nucleotide sequence of a blaKPC-2-harboring plasmid (pKPCAPSS) from Klebsiella pneumoniae ST273 isolated in Saint Petersburg, Russia from a patient with history of recent travel to Vietnam is presented. This 127,970-bp plasmid possessed both IncFII and IncR replicons. blaKPC-2 was localized on a hypothetical mobile element. This element was flanked by 38bp inverted Tn3 repeats and included a Tn3-specific transposase gene, macrolide resistance operon (mphA, mrx, mphR), and a fragment of blaTEM with unique polymorphisms...
December 5, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27914931/valosin-containing-protein-vcp-p97-plays-a-role-in-the-replication-of-west-nile-virus
#3
Wallaya Phongphaew, Shintaro Kobayashi, Michihito Sasaki, Michael Carr, William W Hall, Yasuko Orba, Hirofumi Sawa
Valosin-containing protein (VCP) is classified as a member of the type II AAA(+) ATPase protein family. VCP functions in several cellular processes, including protein degradation, membrane fusion, vesicular trafficking and disassembly of stress granules. Moreover, VCP is considered to play a role in the replication of several viruses, albeit through different mechanisms. In the present study, we have investigated the role of VCP in West Nile virus (WNV) infection. Endogenous VCP expression was inhibited using either VCP inhibitors or by siRNA knockdown...
November 30, 2016: Virus Research
https://www.readbyqxmd.com/read/27895020/a-naturally-occurring-snp-in-plasmid-pb1000-produces-a-reversible-increase-in-antibiotic-resistance
#4
Alfonso Santos-Lopez, Cristina Bernabe-Balas, Manuel Ares-Arroyo, Rafael Ortega-Huedo, Andreas Hoefer, Alvaro San Millan, Bruno Gonzalez-Zorn
ColE1 plasmids are small mobilizable replicons that play an important role in the spread of antibiotic resistance in Pasteurellaceae. In this study we describe how a natural single nucleotide polymorphism (SNP) near the origin of replication of the ColE1-type plasmid pB1000 found in a Pasteurella multocida clinical isolate, generates two independent plasmid variants able to coexist in the same cell simultaneously. Using Haemophilus influenzae Rd strain as a model system, we combined antibiotic susceptibility tests, quantitative PCRs, competition assays and experimental evolution to characterize the consequences of the coexistence of the pB1000 plasmid variants...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27889529/antiviral-activities-of-selected-antimalarials-against-dengue-virus-type-2-and-zika-virus
#5
Anuradha Balasubramanian, Tadahisa Teramoto, Amol A Kulkarni, Apurba K Bhattacharjee, Radhakrishnan Padmanabhan
In a previous study, twelve antimalarial compounds, amodiaquine (AQ) and derivatives, were shown to have potent anti-dengue viral (DENV) activity by using the stable DENV2 Renilla luciferase reporter replicon expressing BHK-21 cells, infectivity (plaque), and the qRT-PCR assays. In this study, we performed molecular modeling on these compounds to determine their stereo-electronic properties required for optimal antiviral activity. Based on the similarity of calculated stereo-electronic profiles, specifically the electrostatic potential profiles of the compounds, and in silico screening of related compounds from literature, we identified three additional compounds, Quinacrine (QC), Mefloquine (MQ), and GSK369796...
November 23, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27885811/17-%C3%AE-estradiol-inhibits-hepatitis-c-virus-mainly-by-interference-with-the-release-phase-of-its-life-cycle
#6
Andrea Magri, Matteo N Barbaglia, Chiara Z Foglia, Elisa Boccato, Michela E Burlone, Sarah Cole, Paola Giarda, Elena Grossini, Arvind H Patel, Rosalba Minisini, Mario Pirisi
BACKGROUND & AIMS: Oestrogen and oestrogen-mediated signalling protect from hepatitis C virus through incompletely understood mechanisms. We aimed to ascertain which phase(s) of hepatitis C virus life cycle is/are affected by oestrogens. METHODS: Huh7 cells infected with the JFH1 virus (genotype 2a) were exposed to dehydroepiandrosterone, testosterone, progesterone and 17β-estradiol (tested with/without its receptor antagonist fulvestrant). Dose-response curves were established to calculate half maximal inhibitory concentration values...
November 7, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/27872077/identification-of-inca-c-plasmid-replication-and-maintenance-genes-and-development-of-a-plasmid-multi-locus-sequence-typing-scheme
#7
Steven J Hancock, Minh-Duy Phan, Kate M Peters, Brian M Forde, Teik Min Chong, Wai-Fong Yin, Kok-Gan Chan, David L Paterson, Timothy R Walsh, Scott A Beatson, Mark A Schembri
Plasmids of incompatibility group IncA/C are becoming increasingly prevalent within pathogenic Enterobacteriaceae. They are associated with the dissemination of multiple clinically relevant resistance genes, including blaCMY and blaNDM Current typing methods for IncA/C plasmids offer limited resolution. In this study, we present the complete sequence of a blaNDM-1-positive IncA/C plasmid, pMS6198A, isolated from a multi-drug resistant uropathogenic Escherichia coli strain. Hyper-saturated transposon mutagenesis, coupled with transposon directed insertion site sequencing (TraDIS) was employed to identify conserved genetic elements required for replication and maintenance of pMS6198A...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27865748/a-novel-reverse-genetics-system-for-production-of-infectious-west-nile-virus-using-homologous-recombination-in-mammalian-cells
#8
Shintaro Kobayashi, Kentaro Yoshii, Minato Hirano, Memi Muto, Hiroaki Kariwa
Reverse genetics systems facilitate investigation of many aspects of the life cycle and pathogenesis of viruses. However, genetic instability in Escherichia coli has hampered development of a reverse genetics system for West Nile virus (WNV). In this study, we developed a novel reverse genetics system for WNV based on homologous recombination in mammalian cells. Introduction of the DNA fragment coding for the WNV structural protein together with a DNA-based replicon resulted in the release of infectious WNV...
November 16, 2016: Journal of Virological Methods
https://www.readbyqxmd.com/read/27860492/veterinary-replicon-vaccines
#9
Mia C Hikke, Gorben P Pijlman
Vaccination is essential in livestock farming and in companion animal ownership. Nucleic acid vaccines based on DNA or RNA provide an elegant alternative to classical veterinary vaccines that have performed suboptimally. Recent advances in terms of rational design, safety, and efficacy have strengthened the position of nucleic acid vaccines in veterinary vaccinology. The present review focuses on replicon vaccines designed for veterinary use. Replicon vaccines are self-amplifying viral RNA sequences that, in addition to the sequence encoding the antigen of interest, contain all elements necessary for RNA replication...
November 14, 2016: Annual Review of Animal Biosciences
https://www.readbyqxmd.com/read/27856044/community-fecal-carriage-of-broad-spectrum-cephalosporin-resistant-escherichia-coli-in-tunisian-children
#10
Sana Ferjani, Mabrouka Saidani, Zeineb Hamzaoui, Carla Andrea Alonso, Carmen Torres, Elaa Maamar, Amine Faouzi Slim, Ben Boubaker Ilhem Boutiba
The spread of extended spectrum β-lactamases (ESBL) and plasmid mediated AmpC β-lactamases (pAmpC) was evaluated in Escherichia coli strains collected from the intestinal microbiota of healthy children in Tunisia. The carriage rate of CTX(R)E. coli was 6.6% (7 of 105 samples) and one strain/sample was further characterized (7 isolates). These isolates harbored blaCTX-M-1 (n = 4), blaCTX-M-15 (n = 2), and blaCMY-2 gene (n = 1), which were usually located on FIB replicon type and carried class 1 integrons. The acc(6')-Ib-cr variant was identified in one isolate that harbored blaCTX-M-15...
March 8, 2016: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/27852861/pre-mrna-processing-factor-prp18-is-a-stimulatory-factor-of-influenza-virus-rna-synthesis-and-possesses-the-np-chaperone-activity
#11
M Minakuchi, K Sugiyama, Y Kato, T Naito, M Okuwaki, A Kawaguchi, K Nagata
: The genome of influenza virus (vRNA) is associated with nucleoprotein (NP) and viral RNA-dependent RNA polymerases, and forms helical viral ribonucleoprotein (vRNP) complexes. NP-vRNA complex is the biologically active template for RNA synthesis by the viral polymerase. Previously, we identified human pre-mRNA processing factor 18 (Prp18) as a stimulatory factor for viral RNA synthesis using an yeast replicon system and single-gene deletion library of yeast (Naito T, Kiyasu Y, Sugiyama K, Kimura A, Nakano R, Matsukage A, Nagata K...
November 16, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27849431/analysis-of-the-relationship-between-enzymatic-and-antiviral-activities-of-the-chicken-oligoadenylate-synthetase-like
#12
Hassan T Tag-El-Din-Hassan, Nobuya Sasaki, Daisuke Torigoe, Masami Morimatsu, Takashi Agui
The oligoadenylate synthetase (OAS) is well known as an antiviral factor against the flavivirus infection in mammals. It is known that the oligoadenylate synthetase-like (ChOAS-L) gene is only present in the chicken genome. It has been shown in the previous report that the ChOAS-L possesses enzymatic activity to convert ATP into 2'-5'-linked oligoadenylates and antiviral activity against West Nile virus (WNV) replicon. Therefore, this study aimed to investigate the relationship between enzymatic and antiviral activities of ChOAS-L...
November 16, 2016: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/27842872/first-detection-of-extended-spectrum-cephalosporin-and-fluoroquinolone-resistant-escherichia-coli-in-australian-food-producing-animals
#13
Sam Abraham, David Jordan, Hui S Wong, James R Johnson, Mark A Toleman, David L Wakeham, David M Gordon, John D Turnidge, Joanne L Mollinger, Justine S Gibson, Darren J Trott
This study aimed to define the frequency of resistance to critically important antimicrobials (CIAs) [i.e. extended-spectrum cephalosporins (ESCs), fluoroquinolones (FQs) and carbapenems] among Escherichia coli isolates causing clinical disease in Australian food-producing animals. Clinical E. coli isolates (n=324) from Australian food-producing animals [cattle (n=169), porcine (n=114), poultry (n=32) and sheep (n=9)] were compiled from all veterinary diagnostic laboratories across Australia over a 1-year period...
December 2015: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/27834610/regional-spread-of-ctx-m-2-producing-proteus-mirabilis-with-the-identical-genetic-structure-in-japan
#14
Karin Kato, Yasufumi Matsumura, Masaki Yamamoto, Miki Nagao, Shunji Takakura, Satoshi Ichiyama
AIMS: In this study, we analyzed the molecular epidemiology of extended-spectrum β-lactamase (ESBL)-producing Proteus mirabilis isolates collected from the central region of Japan. MATERIALS AND METHODS: Between 2005 and 2012, 820 clinical P. mirabilis isolates were obtained from ten acute care hospitals in Japan. We characterized ESBL confirmatory test-positive isolates by sequencing the ESBL genes and their flanking regions, detecting plasmid replicons, and performing pulsed-field gel electrophoresis (PFGE)...
November 11, 2016: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/27827980/replicon-rna-viral-vectors-as-vaccines
#15
REVIEW
Kenneth Lundstrom
Single-stranded RNA viruses of both positive and negative polarity have been used as vectors for vaccine development. In this context, alphaviruses, flaviviruses, measles virus and rhabdoviruses have been engineered for expression of surface protein genes and antigens. Administration of replicon RNA vectors has resulted in strong immune responses and generation of neutralizing antibodies in various animal models. Immunization of mice, chicken, pigs and primates with virus-like particles, naked RNA or layered DNA/RNA plasmids has provided protection against challenges with lethal doses of infectious agents and administered tumor cells...
November 7, 2016: Vaccines
https://www.readbyqxmd.com/read/27827798/unimpaired-immunogenicity-of-yeast-expressed-hepatitis-b-surface-antigen-stored-at-elevated-temperatures
#16
Zhongliang Shen, Yuliang Rao, Shuai Tao, Mengjun Luo, Lijun Ming, Jing Liu, Shaokun Pan, Youhua Xie
Global adoption of hepatitis B virus (HBV) vaccines has greatly reduced new HBV infections. Current HBV vaccines are liquid suspensions containing recombinant hepatitis B surface antigen (HBsAg) particles mixed with aluminum phosphate or aluminum hydroxide. Refrigeration (2-8°C) as recommended for vaccine transport and storage may be unachievable in certain HBV-prevalent developing countries or regions. In this study, we stored yeast-expressed HBsAg and aluminum hydroxide separately at the standard (4°C) and elevated temperature (25, 37, or 45°C) for 14, 23, and 30 days, then mixed them and used the mixture to vaccinate mice with a prime-boost program...
December 2016: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/27822532/is-the-evolution-of-salmonella-enterica-subsp-enterica-linked-to-restriction-modification-systems
#17
Louise Roer, Rene S Hendriksen, Pimlapas Leekitcharoenphon, Oksana Lukjancenko, Rolf Sommer Kaas, Henrik Hasman, Frank M Aarestrup
Salmonella enterica subsp. enterica bacteria are highly diverse foodborne pathogens that are subdivided into more than 1,500 serovars. The diversity is believed to result from mutational evolution, as well as intra- and interspecies recombination that potentially could be influenced by restriction-modification (RM) systems. The aim of this study was to investigate whether RM systems were linked to the evolution of Salmonella enterica subsp. enterica. The study included 221 Salmonella enterica genomes, of which 68 were de novo sequenced and 153 were public available genomes from ENA...
May 2016: MSystems
https://www.readbyqxmd.com/read/27815332/novel-symmetrical-phenylenediamines-as-potential-anti-hepatitis-c-virus-agents
#18
Marcella Bassetto, Salvatore Ferla, Pieter Leyssen, Johan Neyts, Mark M Yerukhimovich, David N Frick, Rachel O'Donnell, Andrea Brancale
BACKGROUND: Despite the great progress made in the last 10 years, alternative strategies might help improving definitive treatment options against hepatitis C virus infection. METHODS: With the aim of identifying novel inhibitors of the hepatitis C virus-1b replication targeting the viral NS3 helicase, the structures of previously reported symmetrical inhibitors of this enzyme were rationally modified, and according to docking-based studies, four novel scaffolds were selected for synthesis and evaluation in the hepatitis C virus-1b subgenomic replicon assay...
November 4, 2016: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/27812150/the-genome-of-the-toluene-degrading-pseudomonas-veronii-strain-1ydbtex2-and-its-differential-gene-expression-in-contaminated-sand
#19
Marian Morales, Vladimir Sentchilo, Claire Bertelli, Andrea Komljenovic, Nadezda Kryuchkova-Mostacci, Audrey Bourdilloud, Burkhard Linke, Alexander Goesmann, Keith Harshman, Francisca Segers, Fabien Delapierre, Damien Fiorucci, Mathieu Seppey, Evgeniya Trofimenco, Pauline Berra, Athimed El Taher, Chloé Loiseau, Dejan Roggero, Madeleine Sulfiotti, Angela Etienne, Gustavo Ruiz Buendia, Loïc Pillard, Angelique Escoriza, Roxane Moritz, Cedric Schneider, Esteban Alfonso, Fatma Ben Jeddou, Oliver Selmoni, Gregory Resch, Gilbert Greub, Olivier Emery, Manupriyam Dubey, Trestan Pillonel, Marc Robinson-Rechavi, Jan Roelof van der Meer
The natural restoration of soils polluted by aromatic hydrocarbons such as benzene, toluene, ethylbenzene and m- and p-xylene (BTEX) may be accelerated by inoculation of specific biodegraders (bioaugmentation). Bioaugmentation mainly involves introducing bacteria that deploy their metabolic properties and adaptation potential to survive and propagate in the contaminated environment by degrading the pollutant. In order to better understand the adaptive response of cells during a transition to contaminated material, we analyzed here the genome and short-term (1 h) changes in genome-wide gene expression of the BTEX-degrading bacterium Pseudomonas veronii 1YdBTEX2 in non-sterile soil and liquid medium, both in presence or absence of toluene...
2016: PloS One
https://www.readbyqxmd.com/read/27810598/in-silico-identification-design-and-synthesis-of-novel-piperazine-based-antiviral-agents-targeting-the-hepatitis-c-virus-helicase
#20
Marcella Bassetto, Pieter Leyssen, Johan Neyts, Mark M Yerukhimovich, David N Frick, Matthew Courtney-Smith, Andrea Brancale
A structure-based virtual screening of commercial compounds was carried out on the HCV NS3 helicase structure, with the aim to identify novel inhibitors of HCV replication. Among a selection of 13 commercial structures, one compound was found to inhibit the subgenomic HCV replicon in the low micromolar range. Different series of new piperazine-based analogues were designed and synthesised, and among them, several novel structures exhibited antiviral activity in the HCV replicon assay. Some of the new compounds were also found to inhibit HCV NS3 helicase function in vitro, and one directly bound NS3 with a dissociation constant of 570 ± 270 nM...
October 23, 2016: European Journal of Medicinal Chemistry
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