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https://www.readbyqxmd.com/read/29772256/extremely-halophilic-pleomorphic-archaeal-virus-hrpv9-extends-the-diversity-of-pleolipoviruses-with-integrases
#1
Nina S Atanasova, Tatiana A Demina, Sudar N V Krishnam Rajan Shanthi, Hanna M Oksanen, Dennis H Bamford
Certain pleomorphic archaeal viruses are highly infectious even at saturated salt. These viruses belong to the genus Betapleolipovirus of the recently described archaeal virus family Pleolipoviridae. Pleolipoviruses comprise single-stranded or double-stranded, circular or linear DNA genomes that share countless homologs among various archaeal genetic elements. Here we describe a new extremely halophilic betapleolipovirus, Halorubrum pleomorphic virus 9 (HRPV9), which has an integrase gene. We also identified new genes encoding minor pleolipoviral structural proteins...
May 14, 2018: Research in Microbiology
https://www.readbyqxmd.com/read/29771694/fostemsavir-a-new-cd4-attachment-inhibitor
#2
Pedro Cahn, Valeria Fink, Patricia Patterson
PURPOSE OF REVIEW: Even in the era of modern HAART, antiretroviral (ARV) failure and emergence of drug resistance is still a problem worldwide. New classes with different mechanisms of action are needed to overcome this challenge. After the integrase inhibitors were launched, more than a decade ago, no new classes were added to the ARV armamentarium. RECENT FINDINGS: Fostemsavir (FTR) is an attachment inhibitor, active regardless of viral tropism, without cross-resistance to any of the existing ARV compounds...
May 15, 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29770748/the-effect-of-switching-protease-inhibitors-to-raltegravir-on-endothelial-function-in-hiv-infected-patients
#3
Maaike Krikke, Kiki Tesselaar, Guido E L van den Berk, Sigrid A Otto, Laura H Freriks, Steven F L van Lelyveld, Frank J L Visseren, Andy I M Hoepelman, Joop E Arends
Objective Lipid management is one of the cornerstones of cardiovascular risk reduction. Treatment of HIV infection with protease inhibitors (PIs) may cause dyslipidaemia, whilst the integrase inhibitor raltegravir (RAL) has a relatively favorable effect on plasma lipids. We examined the effect of switching from PIs to RAL on endothelial function, and its effect on immunological and inflammatory parameters. Methods We performed a 16-week open-label prospective crossover study: 8 weeks intervention (switch PIs to RAL) and 8 weeks control (unchanged cART regimen)...
April 2018: HIV Clinical Trials
https://www.readbyqxmd.com/read/29769116/efficacies-of-cabotegravir-and-bictegravir-against-drug-resistant-hiv-1-integrase-mutants
#4
Steven J Smith, Xue Zhi Zhao, Terrence R Burke, Stephen H Hughes
BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are the class of antiretroviral (ARV) drugs most recently approved by the FDA for the treatment of HIV-1 infections. INSTIs block the strand transfer reaction catalyzed by HIV-1 integrase (IN) and have been shown to potently inhibit infection by wild-type HIV-1. Of the three current FDA-approved INSTIs, Dolutegravir (DTG), has been the most effective, in part because treatment does not readily select for resistant mutants. However, recent studies showed that when INSTI-experienced patients are put on a DTG-salvage therapy, they have reduced response rates...
May 16, 2018: Retrovirology
https://www.readbyqxmd.com/read/29767640/burden-of-exposure-to-potential-interactions-between-antiretroviral-and-non-antiretroviral-medications-in-a-population-of-hiv-positive-patients-aged-50-years-or-older
#5
Alice Ranzani, Letizia Oreni, Massimiliano Agrò, Lorena van den Bogaart, Laura Milazzo, Andrea Giacomelli, Dario Cattaneo, Cristina Gervasoni, Anna Lisa Ridolfo
BACKGROUND: As HIV-infected patients aged 50 years or older are at increased risk of comorbidities and multidrug treatments, we examined their exposure to the potential drug-drug interactions (PDDIs) of antiretroviral (ARV) and other medications. METHODS: This cross-sectional study involved the patients aged 50 years or older receiving ARV and non-ARV medications at our clinic. PDDIs were identified using the University of Liverpool HIV Drug Interaction Checker...
June 1, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29765365/human-activity-determines-the-presence-of-integron-associated-and-antibiotic-resistance-genes-in-southwestern-british-columbia
#6
Miguel I Uyaguari-Díaz, Matthew A Croxen, Zhiyao Luo, Kirby I Cronin, Michael Chan, Waren N Baticados, Matthew J Nesbitt, Shaorong Li, Kristina M Miller, Damion Dooley, William Hsiao, Judith L Isaac-Renton, Patrick Tang, Natalie Prystajecky
The dissemination of antibiotic resistant bacteria from anthropogenic sources into the environment poses an emerging public health threat. Antibiotic resistance genes (ARGs) and gene-capturing systems such as integron-associated integrase genes ( intI ) play a key role in alterations of microbial communities and the spread of antibiotic resistant bacteria into the environment. In order to assess the effect of anthropogenic activities on watersheds in southwestern British Columbia, the presence of putative antibiotic resistance and integrase genes was analyzed in the microbiome of agricultural, urban influenced, and protected watersheds...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29765082/pretreatment-drug-resistance-in-a-large-countrywide-ethiopian-hiv-1c-cohort-a-comparison-of-sanger-and-high-throughput-sequencing
#7
Nigus Fikrie Telele, Amare Worku Kalu, Solomon Gebre-Selassie, Daniel Fekade, Samir Abdurahman, Gaetano Marrone, Ujjwal Neogi, Belete Tegbaru, Anders Sönnerborg
Baseline plasma samples of 490 randomly selected antiretroviral therapy (ART) naïve patients from seven hospitals participating in the first nationwide Ethiopian HIV-1 cohort were analysed for surveillance drug resistance mutations (sDRM) by population based Sanger sequencing (PBSS). Also next generation sequencing (NGS) was used in a subset of 109 baseline samples of patients. Treatment outcome after 6- and 12-months was assessed by on-treatment (OT) and intention-to-treat (ITT) analyses. Transmitted drug resistance (TDR) was detected in 3...
May 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29756689/7-step-flow-synthesis-of-the-hiv-integrase-inhibitor-dolutegravir
#8
Robert E Ziegler, Bimbisar K Desai, Jo-Ann Jee, B Frank Gupton, Thomas D Roper, Timothy F Jamison
Dolutegravir (DTG), an important active pharmaceutical ingredient (API) used in combination therapy for the treatment of HIV, has been synthesized in continuous flow. By adapting the reported GlaxoSmithKline process chemistry batch route for Cabotegravir, DTG was produced in 4.5 h in sequential flow operations from commercially available materials. Key features of the synthesis include rapid manufacturing time for pyridone formation, one-step direct amidation of a functionalized pyridone, and telescoping of multiple steps to avoid isolation of intermediates and enable for greater throughput...
May 14, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29752938/hbv-polymerase-derived-peptide-exerts-an-anti-hiv-1-effect-by-inhibiting-the-acetylation-of-viral-integrase
#9
Hong Kim, So-Young Lee, Yu-Min Choi, Bum-Joon Kim
Here, we found that a 6-mer peptide, Poly6, derived from the hepatitis B virus (HBV), which overlaps with a polymerase corresponding to a preS1 deletion reported to contribute to liver disease progression, can elicit an antiviral effect against human immunodeficiency virus (HIV)-1 by inhibiting HIV-1 integrase (IN) activity of infected cells. Mechanistic studies revealed that the anti-HIV-1 effects of Poly6 occurred via the inhibition of integration, which resulted from the inhibition of acetylation of HIV-1 IN possibly by downregulation of p300 histone acetyltransferase...
May 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29749406/improvement-of-the-activity-of-the-anti-hiv-1-integrase-aptamer-t30175-by-introducing-a-modified-thymidine-into-the-loops
#10
Antonella Virgilio, Teresa Amato, Luigi Petraccone, Francesca Esposito, Nicole Grandi, Enzo Tramontano, Raquel Romero, Shozeb Haider, Isabel Gomez-Monterrey, Ettore Novellino, Luciano Mayol, Veronica Esposito, Aldo Galeone
In this paper, we report our investigations on analogues of the anti-human immunodeficiency virus type 1 (HIV-1) integrase (IN) aptamer T30175 in which the individual thymidines forming the loops were replaced by 5-hydroxymethyl-2'-deoxyuridine residues (H). Circular dichroism, nuclear magnetic resonance and gel electrophoresis investigations clearly indicated that all the modified aptamers preserve the ability to form the original 5'-5' end-stacked head-to-head dimeric G-quadruplex structure, in which each G-quadruplex adopts a parallel arrangement and is characterized by three G-tetrads, three propeller loops and one bulge-loop...
May 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29748498/single-viruses-on-the-fluorescence-microscope-imaging-molecular-mobility-interactions-and-structure-sheds-new-light-on-viral-replication
#11
REVIEW
Nagma Parveen, Doortje Borrenberghs, Susana Rocha, Jelle Hendrix
Viruses are simple agents exhibiting complex reproductive mechanisms. Decades of research have provided crucial basic insights, antiviral medication and moderately successful gene therapy trials. The most infectious viral particle is, however, not always the most abundant one in a population, questioning the utility of classic ensemble-averaging virology. Indeed, viral replication is often not particularly efficient, prone to errors or containing parallel routes. Here, we review different single-molecule sensitive fluorescence methods that we employ routinely to investigate viruses...
May 10, 2018: Viruses
https://www.readbyqxmd.com/read/29746295/the-transition-to-dolutegravir-and-other-new-antiretrovirals-in-low-and-middle-income-countries-what-are-the-issues
#12
Marco Vitoria, Andrew Hill, Nathan Ford, Meg Doherty, Polly Clayden, Francois Venter, David Ripin, Charles Flexner, Paul Domanico
: There are currently approximately 16 million people taking NNRTI-based first-line treatment in low- and middle-income countries. Most of these patients are using the combination of tenofovir (TDF), lamivudine (3TC) and efavirenz (EFV). The integrase inhibitor dolutegravir (DTG) has shown an improved safety profile compared to EFV in randomised studies. DTG also has a high barrier to development of drug resistance. New co-formulated tablets with TDF/3TC/DTG are being introduced into LMICs, for a median price of $75 per person-year...
May 9, 2018: AIDS
https://www.readbyqxmd.com/read/29746268/bictegravir
#13
Vincenzo Spagnuolo, Antonella Castagna, Adriano Lazzarin
PURPOSE OF REVIEW: In this review, we will highlight and discuss the recent efficacy and safety data of bictegravir (BIC), a novel second-generation integrase strand transfer inhibitor (INSTI) that has been recently approved, in coformulation with emtricitabine and tenofovir alafenamide (B/F/TAF), for the treatment of HIV-1 infection in antiretroviral naïve subjects and in those with suppressed viremia. RECENT FINDINGS: Preclinical data showed that BIC has a genetic barrier that is higher than that of raltegravir and elvitegravir but is similar to that of dolutegravir (DTG), with retained activity in vitro against isolates containing substitutions associated with resistance against other INSTIs...
May 4, 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29746267/cabotegravir-its-potential-for-antiretroviral-therapy-and-preexposure-prophylaxis
#14
Hans-Jürgen Stellbrink, Christian Hoffmann
PURPOSE OF REVIEW: Analyzing the evidence for the strand transfer integrase inhibitor cabotegravir (CAB; GSK744, GSK1265744), its properties and differences from other compounds in the class, as well as reviewing the preclinical and clinical evidence for its potential in antretroviral therapy and medical HIV prevention. RECENT FINDINGS: CAB has been investigated both as an oral and an injectable compound. Recent results show that it has promising properties with regards to its potential for parenteral maintenance therapy in combination with other compounds in HIV-infected patients currently suppressed on oral agents, as well as in preexposure prophylaxis...
May 8, 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29741366/metagenomic-characterization-of-antibiotic-resistance-genes-in-full-scale-reclaimed-water-distribution-systems-and-corresponding-potable-systems
#15
Emily Garner, Chaoqi Chen, Kang Xia, Jolene Bowers, David Engelthaler, Jean McLain, Marc A Edwards, Amy Pruden
Water reclamation provides a valuable resource for meeting non-potable water demands. However, little is known about the potential for wastewater reuse to disseminate antibiotic resistance genes (ARGs). Here, samples were collected seasonally in 2014-2015 from four U.S. utilities' reclaimed and potable water distribution systems before treatment, after treatment, and at five points of use (POU). Shotgun metagenomic sequencing was used to profile the resistome (i.e., full contingent of ARGs) of a subset (n=38) of samples...
May 9, 2018: Environmental Science & Technology
https://www.readbyqxmd.com/read/29740520/the-%C3%AE-bt1-large-serine-recombinase-catalyzes-dna-integration-at-pseudo-attb-sites-in-the-genus-nocardia
#16
Marion Herisse, Jessica L Porter, Romain Guerillot, Takehiro Tomita, Anders Goncalves Da Silva, Torsten Seemann, Benjamin P Howden, Timothy P Stinear, Sacha J Pidot
Plasmid vectors based on bacteriophage integrases are important tools in molecular microbiology for the introduction of foreign DNA, especially into bacterial species where other systems for genetic manipulation are limited. Site specific integrases catalyze recombination between phage and bacterial attachment sites ( attP and attB , respectively) and the best studied integrases in the actinomycetes are the serine integrases from the Streptomyces bacteriophages ΦC31 and ΦBT1. As this reaction is unidirectional and highly stable, vectors containing phage integrase systems have been used in a number of genetic engineering applications...
2018: PeerJ
https://www.readbyqxmd.com/read/29735836/association-of-glycerol-kinase-gene-with-class-3-integrons-a-novel-cassette-array-within-escherichia-coli
#17
Rajkumari Elizabeth, Debadatta Dhar Chanda, Atanu Chakravarty, Deepjyoti Paul, Shiela Chetri, Deepshikha Bhowmik, Jayalaxmi Wangkheimayum, Amitabha Bhattacharjee
Background: Integrons are genetic elements which are known for their role in capturing and spreading of antibiotic resistance determinants among Gram-negative bacilli. So far, there is no study regarding Class 3 integron and their genetic organisation in India. Objective: This study investigates the occurrence of Class 3 integron and their gene cassette array among Escherichia coli. Materials and Methods: In this study, a total of 200 E. coli isolates were collected from indoor and outdoor patients from Silchar Medical College and Hospital during September 2015 to February 2016...
January 2018: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29731740/evidence-for-environmental-dissemination-of-antibiotic-resistance-mediated-by-wild-birds
#18
Jiao Wu, Ye Huang, Dawei Rao, Yongkui Zhang, Kun Yang
The aquatic bird, egret, could carry antibiotic resistance (AR) from a contaminated waterway (Jin River, Chengdu, China) into the surrounding environment (Wangjianglou Park). A systematic study was carried out on the unique environmental dissemination mode of AR mediated by birds. The minimum inhibitory concentrations of various antibiotics against the environmental Escherichia coli isolates were used to evaluate the bacterial AR at the environmental locations where these isolates were recovered, i.e., the Jin River water, the egret feces, the park soil, and the campus soil...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29727981/evaluation-of-attenuation-of-pharmaceuticals-toxic-potency-and-antibiotic-resistance-genes-in-constructed-wetlands-treating-wastewater-effluents
#19
Yujie He, Sabri Nurul, Heike Schmitt, Nora B Sutton, Tinka A J Murk, Marco H Blokland, Huub H M Rijnaarts, Alette A M Langenhoff
The performance of constructed wetlands (CWs) in the removal of pharmaceutically active compounds (PhACs) is generally evaluated on the basis of chemical analysis. In this work, we used a combination of chemical, toxicological, and molecular analyses to assess the attenuation of PhACs, toxic potency and antibiotic resistance genes (ARGs) in a field study of three CWs serving as tertiary treatment of wastewater treatment plants. First, 17 PhACs were analysed chemically, of which 14 were detected and seven at concentrations >0...
August 1, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29727296/croi-2018-advances-in-antiretroviral-therapy
#20
Hong-Van Tieu, Barbara S Taylor, Joyce Jones, Timothy J Wilkin
The 2018 Conference on Retroviruses and Opportunistic Infections (CROI) showcased exciting data on new investigational agents including MK-8591 and tri-specific antibody targeting 3 highly conserved epitopes on HIV-1 in a single antibody. Clinical trials of initial antiretroviral therapy (ART) and switch studies involving bictegravir/emtricitabine/tenofovir alafenamide were presented. Intensification of initial ART with integrase strand transfer inhibitors did not increase the risk of immune reconstitution inflammatory syndrome...
May 2018: Topics in Antiviral Medicine
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