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https://www.readbyqxmd.com/read/29444432/surface-matrix-screening-identifies-semi-specific-interactions-that-improve-potency-of-a-near-pan-reactive-hiv-1-neutralizing-antibody
#1
Young D Kwon, Gwo-Yu Chuang, Baoshan Zhang, Robert T Bailer, Nicole A Doria-Rose, Tatyana S Gindin, Bob Lin, Mark K Louder, Krisha McKee, Sijy O'Dell, Amarendra Pegu, Stephen D Schmidt, Mangaiarkarasi Asokan, Xuejun Chen, Misook Choe, Ivelin S Georgiev, Vivian Jin, Marie Pancera, Reda Rawi, Keyun Wang, Rajoshi Chaudhuri, Lisa A Kueltzo, Slobodanka D Manceva, John-Paul Todd, Diana G Scorpio, Mikyung Kim, Ellis L Reinherz, Kshitij Wagh, Bette M Korber, Mark Connors, Lawrence Shapiro, John R Mascola, Peter D Kwong
Highly effective HIV-1-neutralizing antibodies could have utility in the prevention or treatment of HIV-1 infection. To improve the potency of 10E8, an antibody capable of near pan-HIV-1 neutralization, we engineered 10E8-surface mutants and screened for improved neutralization. Variants with the largest functional enhancements involved the addition of hydrophobic or positively charged residues, which were positioned to interact with viral membrane lipids or viral glycan-sialic acids, respectively. In both cases, the site of improvement was spatially separated from the region of antibody mediating molecular contact with the protein component of the antigen, thereby improving peripheral semi-specific interactions while maintaining unmodified dominant contacts responsible for broad recognition...
February 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29444253/hiv-1-genotypic-resistance-testing-using-the-vela-automated-next-generation-sequencing-platform
#2
Stéphanie Raymond, Florence Nicot, Romain Carcenac, Caroline Lefebvre, Nicolas Jeanne, Karine Saune, Pierre Delobel, Jacques Izopet
Objectives: To evaluate the diagnostic performance of the Vela next-generation sequencing (NGS) system in conjunction with the Sentosa SQ HIV Genotyping Assay for genotyping HIV-1. Methods: Plasma RNA was extracted and templates prepared with the Sentosa SX instrument before sequencing the HIV-1 polymerase on the Sentosa SQ301 Sequencer (PGM IonTorrent). The Vela NGS System was compared with direct sequencing and the 454 GS-FLX (Roche) and MiSeq (Illumina) systems for genotypic resistance testing on clinical samples...
February 12, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29443078/chemo-enzymatic-synthesis-of-n-glycans-for-array-development-and-hiv-antibody-profiling
#3
Sachin S Shivatare, Vidya S Shivatare, Chung-Yi Wu, Chi-Huey Wong
We present a highly efficient way for the rapid preparation of a wide range of N-linked oligosaccharides (estimated to exceed 20,000 structures) that are commonly found on human glycoproteins. To achieve the desired structural diversity, the strategy began with the chemo-enzymatic synthesis of three kinds of oligosaccharyl fluoride modules, followed by their stepwise α-selective glycosylations at the 3-O and 6-O positions of the mannose residue of the common core trisaccharide having a crucial β-mannoside linkage...
February 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29442623/structural-characterization-and-analysis-of-human-immunodeficiency-virus-encapsulating-quantum-dots
#4
Wen Yin, Wei Li, Qin Li, Chong Qin, Zhiping Zhang, Xiaowei Zhang, Xian-En Zhang, Zongqiang Cui
Virus internal labeling by inorganic nanoparticle is a suitable technique for single virus imaging. However, it is unknown that the effect of the internal inorganic nanoparticle on morphology and structure of viral core in mature enveloped Human immunodeficiency virus 1 (HIV-1). Also, the analysis of intact HIV-1 particles and virus-inorganic nanoparticle hybrids is almost impossible with conventional negative staining because HIV-1 is inherently fragile and unstable. Herein, we carried out morphological and structural analysis of a newly constructed quantum dot (QD)-encapsulated infectious HIV-1 particle by using an optimized procedure for the electron microscopic analysis of negatively stained HIV-1 particles...
July 1, 2018: Journal of Nanoscience and Nanotechnology
https://www.readbyqxmd.com/read/29442543/dolutegravir-dual-therapy-as-maintenance-treatment-in-hiv-infected-patients-a-review
#5
Rosaleen Boswell, Michelle M Foisy, Christine A Hughes
OBJECTIVE: To review available evidence for dolutegravir-based dual therapy as maintenance treatment in HIV-1 infected patients. DATA SOURCES: A literature search was conducted using PubMed, MEDLINE, and Google Scholar to the end of January 2018. Conference abstracts and article bibliographies were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All English-language, randomized, and observational studies were included. DATA SYNTHESIS: In all, 12 studies were identified: 10 were observational, and 2 were randomized trials...
February 1, 2018: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/29441145/epigenetic-regulation-of-hiv-1-latency-focus-on-polycomb-group-pcg-proteins
#6
REVIEW
Sheraz Khan, Mazhar Iqbal, Muhammad Tariq, Shahid M Baig, Wasim Abbas
HIV-1 latency allows the virus to persist until reactivation, in a transcriptionally silent form in its cellular reservoirs despite the presence of effective cART. Such viral persistence represents a major barrier to HIV eradication since treatment interruption leads to rebound plasma viremia. Polycomb group (PcG) proteins have recently got a considerable attention in regulating HIV-1 post-integration latency as they are involved in the repression of proviral gene expression through the methylation of histones...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29439644/potential-hiv-1-fusion-inhibitors-mimicking-gp41-specific-broadly-neutralizing-antibody-10e8-in-silico-discovery-and-prediction-of-antiviral-potency
#7
Alexander M Andrianov, Ivan A Kashyn, Alexander V Tuzikov
An integrated computational approach to in silico drug design was used to identify novel HIV-1 fusion inhibitor scaffolds mimicking broadly neutralizing antibody (bNab) 10E8 targeting the membrane proximal external region (MPER) of the HIV-1 gp41 protein. This computer-based approach included (i) generation of pharmacophore models representing 3D-arrangements of chemical functionalities that make bNAb 10E8 active towards the gp41 MPER segment, (ii) shape and pharmacophore-based identification of the 10E8-mimetic candidates by a web-oriented virtual screening platform pepMMsMIMIC, (iii) high-throughput docking of the identified compounds with the gp41 MPER peptide, and (iv) molecular dynamics simulations of the docked structures followed by binding free energy calculations...
January 15, 2018: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/29439583/identification-of-a-novel-hiv-1-recombinant-form-b-c-in-men-who-have-sex-with-men-in-shaanxi-china
#8
Mengyan Zhang, Ruolei Xin, Wenhui Chang
Many new circulating recombinant forms (CRFs) and unique recombinant forms (URFs) of HIV-1 have been found in men who have sex with men (MSM) in recent years, in China. In this study, a unique HIV-1 recombinant genome (SN153) was characterized from an HIV-positive male infected through homosexual behavior in Shaanxi, China. The mosaic pattern had a complex intersubtype recombinant structure with six breakpoints, with three subtype C segments inserted into subtype B backbone. And three similar breakpoints with CRF07_BC were observed in the pol gene...
February 14, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29439582/diversity-of-hiv-1-in-aquitaine-south-western-france-2012-2016
#9
Camille Tumiotto, Pantxika Bellecave, Patricia Recordon-Pinson, Alexi Groppi, Macha Nikolski, Herve J Fleury
We have estimated the prevalence of the different viral subtypes between January 2012 and December 2016 in HIV-1-infected patients of the Aquitaine region (south-west part of France) who had a routine HIV-1 genotype resistance testing (GRT) centralized at the Bordeaux University Hospital. GRT was performed on viral RNA (1784 samples) before treatment initiation or at failure whereas proviral DNA was used as template (1420 samples) in the event of a treatment switch in patients with viral load below 50 copies/mL...
February 14, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29438560/hiite-hiv-1-incidence-and-infection-time-estimator
#10
Sung Yong Park, Tanzy M T Love, Shivankur Kapoor, Ha Youn Lee, John Hancock
Motivation: Around 2.1 million new HIV-1 infections were reported in 2015, alerting that the HIV-1 epidemic remains a significant global health challenge. Precise incidence assessment strengthens epidemic monitoring efforts and guides strategy optimization for prevention programs. Estimating the onset time of HIV-1 infection can facilitate optimal clinical management and identify key populations largely responsible for epidemic spread and thereby infer HIV-1 transmission chains. Our goal is to develop a genomic assay estimating the incidence and infection time in a single cross-sectional survey setting...
February 9, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29438200/switching-from-abacavir-to-tenofovir-disoproxil-fumarate-is-associated-with-rises-in-soluble-glycoprotein-vi-suggesting-changes-in-platelet-collagen-interactions
#11
Jane A O'Halloran, Eimear Dunne, Willard Tinago, Stephanie Denieffe, Dermot Kenny, Patrick W G Mallon
OBJECTIVES: Altered platelet function has been proposed as an underlying mechanism to explain increased risk of myocardial infarction in people living with HIV associated with use of the nucleoside reverse transcriptase inhibitor abacavir (ABC). We aimed to examine changes in platelet biomarkers in people living with HIV switching from ABC. METHODS: In a prospective, 48-week substudy of virally suppressed HIV-1-positive subjects randomized to remain on ABC/lamivudine (ABC/3TC) or switch to tenofovir disoproxil fumarate/emtricitabine, we measured soluble glycoprotein VI (sGPVI), soluble P-selectin, soluble CD40 ligand and von Willebrand factor in plasma collected over time and assessed differences using mixed effect models...
February 12, 2018: AIDS
https://www.readbyqxmd.com/read/29438196/antiretroviral-drug-concentrations-in-hair-are-associated-with-virologic-outcomes-among-young-people-living-with-hiv-in-tanzania
#12
Zachary J Tabb, Blandina T Mmbaga, Monica Gandhi, Alexander Louie, Karen Kuncze, Hideaki Okochi, Aisa M Shayo, Elizabeth L Turner, Coleen K Cunningham, Dorothy E Dow
OBJECTIVE: We assessed the relationship of self-reported adherence versus antiretroviral therapy (ART) concentrations in hair with virologic outcomes among young people living with HIV. DESIGN: This was a cross-sectional study that enrolled young people living with HIV age 11-24 years, who attended a youth HIV clinic in Moshi, Tanzania. METHODS: ART adherence was assessed by self-report, drug concentration in hair samples, and plasma HIV-1 RNA measurements...
February 12, 2018: AIDS
https://www.readbyqxmd.com/read/29438122/corneal-and-anterior-chamber-morphology-in-human-immunodeficiency-virus-1-infected-patients-without-opportunistic-infections
#13
Ebru N Cetin, Selda Sayın Kutlu, Osman Parca, Murat Kutlu, Gökhan Pekel
OBJECTIVES: To evaluate corneal and anterior chamber morphology as measured by Pentacam HR in human immunodeficiency virus (HIV)-infected patients without opportunistic infections and to search for signs of accelerated aging. METHODS: This prospective study included 41 eyes of 41 HIV-1-infected patients (study group) and 50 eyes of 50 healthy subjects (control group). Specular microscope and Pentacam HR were used for corneal and anterior chamber morphology evaluation...
February 12, 2018: Eye & Contact Lens
https://www.readbyqxmd.com/read/29437967/immunogenicity-of-nyvac-prime-protein-boost-hiv-1-envelope-vaccination-and-shiv-challenge-of-nonhuman-primates
#14
Kevin O Saunders, Sampa Santra, Robert Parks, Nicole L Yates, Laura L Sutherland, Richard M Scearce, Harikrishnan Balachandran, Todd Bradley, Derrick Goodman, Amanda Eaton, Sherry A Stanfield-Oakley, James Tartaglia, Sanjay Phogat, Giuseppe Pantaleo, Mariano Esteban, Carmen E Gomez, Beatriz Perdiguero, Bertram Jacobs, Karen Kibler, Bette Korber, David C Montefiori, Guido Ferrrari, Nathan Vandergrift, Hua-Xin Liao, Georgia D Tomaras, Barton F Haynes
A preventive HIV-1 vaccine is an essential part of the strategy to eradicate AIDS. A critical question is whether antibodies that do not neutralize primary isolate (tier 2) HIV-1 viruses can protect from infection. Here, we investigated the ability of an attenuated poxvirus vector (NYVAC) prime-envelope gp120 boost to elicit potentially protective antibody responses in a rhesus macaque model of mucosal simian-human immunodeficiency virus (SHIV) infection. NYVAC vector delivery of a group M consensus envelope, trivalent mosaic envelopes, or a natural clade B isolate B...
February 7, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29437904/a-computational-study-for-rational-hiv-1-non-nucleoside-reverse-transcriptase-inhibitor-selection-and-discovery-of-novel-allosteric-pockets-for-inhibitor-design
#15
Ron Zhi-Hui Chiang, Samuel Ken-En Gan, Chinh Tran-To Su
HIV drug resistant mutations that render the current Highly Active Anti-Retroviral Therapy cocktail drugs ineffective are increasingly reported. To study the mechanisms of these mutations in conferring drug resistance, we computationally analyzed fourteen Reverse Transcriptase (RT) structures of HIV-1 on the following parameters: drug-binding pocket volume, allosteric effects caused by the mutations, and structural thermal stability. We constructed structural correlation-based networks of the mutant RT-drug complexes and the analyses support the use of Efavirenz as the first-line drug, given that cross-resistance is least likely to develop from Efavirenz-resistant mutations...
February 5, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29437300/design-of-highly-potent-dual-acting-and-central-nervous-system-penetrating-hiv-1-protease-inhibitors-with-excellent-potency-against-multidrug-resistant-hiv-1-variants
#16
Arun K Ghosh, Kalapala Venkateswara Rao, Prasanth R Nyalapatla, Satish Kovela, Margherita Brindisi, Heather L Osswald, Bhavanam Sekhara Reddy, Johnson Agniswamy, Yuan-Fang Wang, Manabu Aoki, Shin-Ichiro Hattori, Irene T Weber, Hiroaki Mitsuya
We report here the design, synthesis, X-ray-structural, and biological studies of an exceptionally potent HIV-1 protease inhibitor 5. In this inhibitor, we incorporated an unprecedented structure-based designed 6-5-5-ring fused crown-like tetrahydropyranofuran as the P2-ligand, a cyclopropylaminobenzothiazole as the P2'-ligand and 3,5-difluorophenylmethyl as the P1-ligand. The resulting inhibitor 5, exhibited exceptional HIV-1 inhibitory and antiviral potency at picomolar level. Furthermore, it displayed antiviral IC50 values in picomolar range against a wide panel of highly multidrug-resistant HIV-1 variants...
February 13, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29437254/crispr-cas9-knockout-of-usp18-enhances-type-i-ifn-responsiveness-and-restricts-hiv-1-infection-in-macrophages
#17
Jared P Taylor, Melanie N Cash, Katherine E Santostefano, Mahito Nakanishi, Naohiro Terada, Mark A Wallet
The IFN-stimulated gene ubiquitin-specific proteinase 18 (USP18) encodes a protein that negatively regulates T1 IFN signaling via stearic inhibition of JAK1 recruitment to the IFN-α receptor 2 subunit (IFNAR2). Here, we demonstrate that USP18 expression is induced by HIV-1 in a T1 IFN-dependent manner. Experimental depletion of USP18 by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing results in a significant restriction of HIV-1 replication in an induced pluripotent stem cell (iPSC)-derived macrophage model...
February 13, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29436843/synthesis-and-substrate-properties-towards-hiv-1-reverse-transcriptase-of-new-diphosphate-analogues-of-9-2-phosphonomethoxy-ethyl-adenine
#18
Wolfgang Hg Laux, Stéphane Priet, Karine Alvarez, Suzanne Peyrottes, Christian Périgaud
Background The replacement of β,γ-pyrophosphate by β,γ-phosphonate moieties within the triphosphate chain of 5'-triphosphate nucleoside analogues was previously studied for various antiviral nucleoside analogues such as AZT and 2',3'-dideoxynucleosides. Thus, it has been shown that these chemical modifications could preserve, in some cases, the terminating substrate properties of the triphosphate analogue for HIV-RT. Herein, we aimed to study such 5'-triphosphate mimics based on the scaffold of the well-known antiviral agent 9-[(2-phosphonomethoxy)ethyl]adenine (PMEA, Adefovir)...
January 2018: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/29435709/the-prevalence-and-isolated-subtypes-of-bk-polyomavirus-reactivation-among-patients-infected-with-human-immunodeficiency-virus-1-in-southeastern-china
#19
Caiqin Hu, Ying Huang, Juwei Su, Mengyan Wang, Qihui Zhou, Biao Zhu
BK polyomavirus (BKPyV) is an opportunistic infectious pathogen that is associated with hemorrhagic cystitis and nephropathy, mainly in transplant recipients and human immunodeficiency virus 1 (HIV-1) infected patients. However, molecular characterization studies of BKPyV in China are rare. This study was designed to elucidate the prevalence and to determine the main subtypes of BKPyV among HIV-1-infected patients in southeastern China. In addition, the increased incidences for BKPyV reactivation were analyzed...
February 12, 2018: Archives of Virology
https://www.readbyqxmd.com/read/29435471/hiv-1-drug-resistance-and-third-line-therapy-outcomes-in-patients-failing-second-line-therapy-in-zimbabwe
#20
Cleophas Chimbetete, David Katzenstein, Tinei Shamu, Adrian Spoerri, Janne Estill, Matthias Egger, Olivia Keiser
Objectives: To analyze the patterns and risk factors of HIV drug resistance mutations among patients failing second-line treatment and to describe early treatment responses to recommended third-line antiretroviral therapy (ART) in a national referral HIV clinic in Zimbabwe. Methods: Patients on boosted protease inhibitor (PI) regimens for more than 6 months with treatment failure confirmed by 2 viral load (VL) tests >1000 copies/mL were genotyped, and susceptibility to available antiretroviral drugs was estimated by the Stanford HIVdb program...
February 2018: Open Forum Infectious Diseases
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