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https://www.readbyqxmd.com/read/28918033/six-highly-conserved-targets-of-rnai-revealed-in-hiv-1-infected-patients-from-russia-are-also-present-in-many-hiv-1-strains-worldwide
#1
Olga V Kretova, Daria M Fedoseeva, Maria A Gorbacheva, Natalya M Gashnikova, Maria P Gashnikova, Nataliya V Melnikova, Vladimir R Chechetkin, Yuri V Kravatsky, Nickolai A Tchurikov
RNAi has been suggested for use in gene therapy of HIV/AIDS, but the main problem is that HIV-1 is highly variable and could escape attack from the small interfering RNAs (siRNAs) due to even single nucleotide substitutions in the potential targets. To exhaustively check the variability in selected RNA targets of HIV-1, we used ultra-deep sequencing of six regions of HIV-1 from the plasma of two independent cohorts of patients from Russia. Six RNAi targets were found that are invariable in 82%-97% of viruses in both cohorts and are located inside the domains specifying reverse transcriptase (RT), integrase, vpu, gp120, and p17...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28915327/adipose-tissue-in-hiv-infection
#2
John R Koethe
HIV infection and antiretroviral therapy (ART) treatment exert diverse effects on adipocytes and stromal-vascular fraction cells, leading to changes in adipose tissue quantity, distribution, and energy storage. A HIV-associated lipodystrophic condition was recognized early in the epidemic, characterized by clinically apparent changes in subcutaneous, visceral, and dorsocervical adipose depots. Underlying these changes is altered adipose tissue morphology and expression of genes central to adipocyte maturation, regulation, metabolism, and cytokine signaling...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28914817/ledgf-p75-deficiency-increases-deletions-at-the-hiv-1-cdna-ends
#3
Murilo T D Bueno, Daniel Reyes, Manuel Llano
Processing of unintegrated linear HIV-1 cDNA by the host DNA repair system results in its degradation and/or circularization. As a consequence, deficient viral cDNA integration generally leads to an increase in the levels of HIV-1 cDNA circles containing one or two long terminal repeats (LTRs). Intriguingly, impaired HIV-1 integration in LEDGF/p75-deficient cells does not result in a correspondent increase in viral cDNA circles. We postulate that increased degradation of unintegrated linear viral cDNA in cells lacking the lens epithelium-derived growth factor (LEDGF/p75) account for this inconsistency...
September 15, 2017: Viruses
https://www.readbyqxmd.com/read/28911112/integrative-and-conjugative-elements-and-their-hosts-composition-distribution-and-organization
#4
Jean Cury, Marie Touchon, Eduardo P C Rocha
Conjugation of single-stranded DNA drives horizontal gene transfer between bacteria and was widely studied in conjugative plasmids. The organization and function of integrative and conjugative elements (ICE), even if they are more abundant, was only studied in a few model systems. Comparative genomics of ICE has been precluded by the difficulty in finding and delimiting these elements. Here, we present the results of a method that circumvents these problems by requiring only the identification of the conjugation genes and the species' pan-genome...
September 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28905222/a-single-center-retrospective-cohort-analysis-of-maternal-and-infant-outcomes-in-hiv-infected-mothers-treated-with-integrase-inhibitors-during-pregnancy
#5
Monique L Mounce, Laura Pontiggia, Jessica L Adams
INTRODUCTION: Integrase strand transfer inhibitors (INSTI) are currently being investigated for the treatment of HIV in pregnancy. The purpose of this study is to evaluate the differences in maternal and infant outcomes in HIV-positive mothers treated with INSTI-containing antiretroviral therapy (ART) during pregnancy compared to protease inhibitor (PI)-containing ART. METHODS: A retrospective, cohort study of INSTI- and PI-based ART used in pregnancy between 2007 and 2015 was performed...
September 13, 2017: Infectious Diseases and Therapy
https://www.readbyqxmd.com/read/28904565/class-1-integrons-and-plasmid-mediated-multiple-resistance-genes-of-the-campylobacter-species-from-pediatric-patient-of-a-university-hospital-in-taiwan
#6
Yi-Chih Chang, Ni Tien, Jai-Sing Yang, Chi-Cheng Lu, Fuu-Jen Tsai, Tsurng-Juhn Huang, I-Kuan Wang
BACKGROUND: The Campylobacter species usually causes infection between humans and livestock interaction via livestock breeding. The studies of the Campylobacter species thus far in all clinical isolates were to show the many kinds of antibiotic phenomenon that were produced. Their integrons cause the induction of antibiotic resistance between bacterial species in the Campylobacter species. RESULTS: The bacterial strains from the diarrhea of pediatric patient which isolated by China Medical University Hospital storage bank...
2017: Gut Pathogens
https://www.readbyqxmd.com/read/28904329/latest-advances-in-the-efficacy-tolerability-and-monotherapy-of-integrase-inhibitors
#7
Qi Tang, Hongzhou Lu
More than 30 drugs for antiretroviral therapy (ART), including integrase inhibitors (INIs), have been approved by the U.S. Food and Drug Administration (FDA) as of 2017. Integrase is the third essential enzyme in the cycle of human immunodeficiency virus (HIV) replication. INIs can effectively inhibit the replication of HIV and HIV is less prone to develop resistance to INIs clinically. Previous studies based on 7 phase III clinic trials indicate that INIs have satisfactory efficacy and tolerability in patients infected with HIV...
2017: Bioscience Trends
https://www.readbyqxmd.com/read/28901212/a-retrospective-clinical-audit-of-general-practices-in-australia-to-determine-the-motivation-for-switch-to-dolutegravir-abacavir-lamivudine-and-clinical-outcomes
#8
Pedro E Ferrer, Mark Bloch, Norman Roth, Robert Finlayson, David Baker, Ken Koh, David Orth, Rimgaile Urbaityte, Dannae Brown, Fraser Drummond
The most common reasons for switching HIV-1 therapy in patients with virologic suppression are treatment regimen simplification and resolving tolerability issues. Single-pill regimens that include an integrase inhibitor are recommended options. A retrospective clinical audit was performed to determine the motivations for switching to dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC) at high HIV-caseload general practice clinics in Australia. The most common reasons for switching from a prior suppressive therapy to DTG/ABC/3TC were simplification of regimen, resolving toxicity/intolerance and patient preference (73%, 13% and 12%, respectively)...
January 1, 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/28898391/recoding-of-synonymous-genes-to-expand-evolutionary-landscapes-requires-control-of-secondary-structure-affecting-translation
#9
Jose Antonio Escudero, Aleksandra Nivina, Guillaume Cambray, Rocío López-Igual, Celine Loot, Didier Mazel
Synthetic DNA design needs to harness the many information layers embedded in a DNA string. We previously developed the Evolutionary Landscape Painter (ELP), an algorithm that exploits the degeneracy of the code to increase protein evolvability. Here, we have used ELP to recode the integron integrase gene (intI1) in two alternative alleles. Although synonymous, both alleles yielded less IntI1 protein and were less active in recombination assays than intI1. We spliced the three alleles and mapped the activity decrease to the beginning of alternative sequences...
September 12, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28893775/a-nosocomial-outbreak-of-extensively-drug-resistant-xdr-acinetobacter-baumannii-isolates-containing-blaoxa-237-encoded-on-a-plasmid
#10
Andrea M Hujer, Paul G Higgins, Susan D Rudin, Genevieve L Buser, Steven H Marshall, Kyriaki Xanthopoulou, Harald Seifert, Laura J Rojas, T Nicholas Domitrovic, P Maureen Cassidy, Margaret C Cunningham, Robert Vega, Jon P Furuno, Christopher D Pfeiffer, Zintars G Beldavs, Meredith S Wright, Michael R Jacobs, Mark D Adams, Robert A Bonomo
Carbapenem antibiotics are among the mainstay for treating infections caused by Acinetobacter baumannii, especially in the Northwest United States where carbapenem resistant A. baumannii remain relatively rare. However, between June 2012 and October 2014, an outbreak of carbapenem-resistant A. baumannii occurred in 16 patients from 5 healthcare facilities in the state of Oregon. All isolates were defined as extensively-drug resistant (XDR). MLST revealed that the isolates belonged to sequence type 2 (international clone 2, IC2), and were greater than 95% similar by rep-PCR analysis...
September 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28893321/prevalence-and-trends-in-transmitted-and-acquired-antiretroviral-drug-resistance-washington-dc-1999-2014
#11
Annette M Aldous, Amanda D Castel, David M Parenti
BACKGROUND: Drug resistance limits options for antiretroviral therapy (ART) and results in poorer health outcomes among HIV-infected persons. We sought to characterize resistance patterns and to identify predictors of resistance in Washington, DC. METHODS: We analyzed resistance in the DC Cohort, a longitudinal study of HIV-infected persons in care in Washington, DC. We measured cumulative drug resistance (CDR) among participants with any genotype between 1999 and 2014 (n = 3411), transmitted drug resistance (TDR) in ART-naïve persons (n = 1503), and acquired drug resistance (ADR) in persons with genotypes before and after ART initiation (n = 309)...
September 11, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28891788/week-48-resistance-analysis-of-elvitegravir-cobicistat-emtricitabine-tenofovir-df-versus-atazanavir-ritonavir-emtricitabine-tenofovir-df-in-hiv-1-infected-women-waves-study-gs-us-236-0128
#12
Rima Kulkarni, Sally L Hodder, Huyen Cao, Silvia Chang, Michael D Miller, Kirsten L White
Background Women and those with non-B subtype HIV-1 are typically underrepresented in clinical trials. WAVES (GS-US-236-0128) was a double-blind phase 3b study among treatment-naïve HIV-1-infected women that demonstrated that elvitegravir/cobicistat/emtricitabine/tenofovir DF (EVG/COBI/FTC/TDF; N = 289) was superior to atazanavir + ritonavir + FTC/TDF (ATV + RTV + FTC/TDF; N = 286) for HIV-1 RNA < 50 copies/mL by FDA snapshot analysis at week 48. Here, we describe resistance development through week 48 in women with virologic failure and determine the impact of pre-existing mutations and HIV-1 subtype on viral suppression...
July 2017: HIV Clinical Trials
https://www.readbyqxmd.com/read/28890197/revisiting-asthma-therapeutics-focus-on-wnt-signal-transduction
#13
REVIEW
Tim Koopmans, Reinoud Gosens
Asthma is a complex disease of the airways that develops as a consequence of both genetic and environmental factors. This interaction has highlighted genes important in early life, particularly those that control lung development, such as the Wingless/Integrase-1 (WNT) signalling pathway. Although aberrant WNT signalling is involved with an array of human conditions, it has received little attention within the context of asthma. Yet it is highly relevant, driving events involved with inflammation, airway remodelling, and airway hyper-responsiveness (AHR)...
September 7, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28886881/pahs-accelerate-the-propagation-of-antibiotic-resistance-genes-in-coastal-water-microbial-community
#14
Jing Wang, Jing Wang, Zelong Zhao, Jingwen Chen, Hong Lu, Guangfei Liu, Jiti Zhou, Xiaoyan Guan
Antibiotic resistance genes (ARGs) have been regarded as emerging contaminants and have attracted growing attention owing to their widespread presence in the environment. In addition to the well-documented selective pressure of antibiotics, ARGs have also become prevalent because of anthropogenic impacts. Coastal habitats are located between terrestrial and marine ecosystems, which are a hotspot for anthropogenic impacts. Excessive accumulation of polycyclic aromatic hydrocarbons (PAHs) has posed a serious threat to coastal habitats, but no information is available on the effect of PAHs on antibiotic resistance in the microbial community of coastal environments...
September 6, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28882882/how-i-treat-patients-with-hiv-related-hematological-malignancies-using-hematopoietic-cell-transplantation
#15
Joseph C Alvarnas, John A Zaia, Stephen J Forman
Hematopoietic cell transplantation (HCT) has now been shown to be safe and effective for selected HIV-infected patients with hematological malignancies. Autologous HCT is now standard of care for patients with HIV-related lymphomas who otherwise meet standard transplant criteria. Limited data also supports use of allogeneic HCT (alloHCT) in selected HIV-infected patients who meet standard transplant criteria. We recommend enrolling patients on clinical trials that offer access to CCR5Δ32 homozygous donors, if available...
September 7, 2017: Blood
https://www.readbyqxmd.com/read/28881722/hepatic-nk-cell-mediated-hypersensitivity-to-cona-induced-liver-injury-in-mouse-liver-expressing-hepatitis-c-virus-polyprotein
#16
Qiuxia Fu, Shaoduo Yan, Licui Wang, Xiangguo Duan, Lei Wang, Yue Wang, Tao Wu, Xiaohui Wang, Jie An, Yulong Zhang, Qianqian Zhou, Linsheng Zhan
The role of hepatic NK cells in the pathogenesis of HCV-associated hepatic failure is incompletely understood. In this study, we investigated the effect of HCV on ConA-induced immunological hepatic injury and the influence of HCV on hepatic NK cell activation in the liver after ConA administration. An immunocompetent HCV mouse model that encodes the entire viral polyprotein in a liver-specific manner based on hydrodynamic injection and φC31o integrase was used to study the role of hepatic NK cells. Interestingly, the frequency of hepatic NK cells was reduced in HCV mice, whereas the levels of other intrahepatic lymphocytes remained unaltered...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28869593/how-type-ii-crispr-cas-establish-immunity-through-cas1-cas2-mediated-spacer-integration
#17
Yibei Xiao, Sherwin Ng, Ki Hyun Nam, Ailong Ke
CRISPR (clustered regularly interspaced short palindromic repeats) and the nearby cas (CRISPR-associated) operon establish an RNA-based adaptive immunity system in prokaryotes(1-5). Molecular memory is created when a short foreign DNA-derived prespacer is integrated into the CRISPR array as a new spacer(6-9). Whereas the RNA-guided CRISPR interference mechanism varies widely among CRISPR-Cas systems, the spacer integration mechanism is essentially identical(7-9). The conserved Cas1 and Cas2 proteins form an integrase complex consisting two distal Cas1 dimers bridged by a Cas2 dimer in the middle(6,10)...
September 4, 2017: Nature
https://www.readbyqxmd.com/read/28867499/coformulated-bictegravir-emtricitabine-and-tenofovir-alafenamide-versus-dolutegravir-with-emtricitabine-and-tenofovir-alafenamide-for-initial-treatment-of-hiv-1-infection-gs-us-380-1490-a-randomised-double-blind-multicentre-phase-3-non-inferiority-trial
#18
Paul E Sax, Anton Pozniak, M Luisa Montes, Ellen Koenig, Edwin DeJesus, Hans-Jürgen Stellbrink, Andrea Antinori, Kimberly Workowski, Jihad Slim, Jacques Reynes, Will Garner, Joseph Custodio, Kirsten White, Devi SenGupta, Andrew Cheng, Erin Quirk
BACKGROUND: Integrase strand transfer inhibitors (INSTIs) coadministered with two nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) are recommended as first-line treatment for HIV, and coformulated fixed-dose combinations are preferred to facilitate adherence. We report 48-week results from a study comparing initial HIV-1 treatment with bictegravir-a novel INSTI with a high in-vitro barrier to resistance and low potential as a perpetrator or victim of clinically relevant drug interactions-coformulated with the NRTI combination emtricitabine and tenofovir alafenamide as a fixed-dose combination to dolutegravir administered with coformulated emtricitabine and tenofovir alafenamide...
August 31, 2017: Lancet
https://www.readbyqxmd.com/read/28867497/bictegravir-emtricitabine-and-tenofovir-alafenamide-versus-dolutegravir-abacavir-and-lamivudine-for-initial-treatment-of-hiv-1-infection-gs-us-380-1489-a-double-blind-multicentre-phase-3-randomised-controlled-non-inferiority-trial
#19
Joel Gallant, Adriano Lazzarin, Anthony Mills, Chloe Orkin, Daniel Podzamczer, Pablo Tebas, Pierre-Marie Girard, Indira Brar, Eric S Daar, David Wohl, Jürgen Rockstroh, Xuelian Wei, Joseph Custodio, Kirsten White, Hal Martin, Andrew Cheng, Erin Quirk
BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are recommended components of initial antiretroviral therapy with two nucleoside reverse transcriptase inhibitors. Bictegravir is a novel, potent INSTI with a high in-vitro barrier to resistance and low potential as a perpetrator or victim of clinically relevant drug-drug interactions. We aimed to assess the efficacy and safety of bictegravir coformulated with emtricitabine and tenofovir alafenamide as a fixed-dose combination versus coformulated dolutegravir, abacavir, and lamivudine...
August 31, 2017: Lancet
https://www.readbyqxmd.com/read/28861811/differential-effects-of-antiretroviral-drugs-on-neurons-in-vitro-roles-for-oxidative-stress-and-integrated-stress-response
#20
Anna L Stern, Rebecca N Lee, Nina Panvelker, Jiean Li, Jenna Harowitz, Kelly L Jordan-Sciutto, Cagla Akay-Espinoza
Mounting evidence suggests that antiretroviral drugs may contribute to the persistence of HIV-associated neurocognitive disorders (HAND), which impact 30%-50% of HIV-infected patients in the post-antiretroviral era. We previously reported that two first generation HIV protease inhibitors, ritonavir and saquinavir, induced oxidative stress, with subsequent neuronal death in vitro, which was reversed by augmentation of the endogenous antioxidant response by monomethyl fumarate. We herein determined whether two newer-generation PIs, darunavir and lopinavir, were deleterious to neurons in vitro...
August 31, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
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