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https://www.readbyqxmd.com/read/28822154/-a-new-benzamide-derivative-from-rice-fermentation-of-streptomyces-sp-cpcc-202950
#1
Shan-Shan Chang, Ming-Hua Chen, Ren-Zhong Wang, Ye-Xiang Wu, Guo-Hong Yang, Biao Dong, Li-Yan Yu, Zeng-Ping Gao, Shu-Yi Si
Eight compounds were isolated from the rice fermentation of Streptomyces sp. CPCC 202950 by a combination of various chromatographic techniques including column chromatography over silica, Sephadex LH-20, flash C₁₈, and reversed-phase HPLC. Their structures were identified as 3-[(3'-amino-3'-oxoprop-1'-en-2'-yl)oxy]benzamide (1), m-hydroxybenzamide (2), leptosphaepin (3), 5-methyluracil (4), feruloylamide (5), p-hydroxyphenylacetoamide (6), vanillamide (7), cyclo (L-val-L-ala) (8). Among them, 1 was a new benzamide analogue, and 2 was a new natural product...
June 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28819312/shared-peptide-binding-of-hla-class-i-and-ii-alleles-associate-with-cutaneous-nevirapine-hypersensitivity-and-identify-novel-risk-alleles
#2
Rebecca Pavlos, Elizabeth J McKinnon, David A Ostrov, Bjoern Peters, Soren Buus, David Koelle, Abha Chopra, Ryan Schutte, Craig Rive, Alec Redwood, Susana Restrepo, Austin Bracey, Thomas Kaever, Paisley Myers, Ellen Speers, Stacy A Malaker, Jeffrey Shabanowitz, Yuan Jing, Silvana Gaudieri, Donald F Hunt, Mary Carrington, David W Haas, Simon Mallal, Elizabeth J Phillips
Genes of the human leukocyte antigen (HLA) system encode cell-surface proteins involved in regulation of immune responses, and the way drugs interact with the HLA peptide binding groove is important in the immunopathogenesis of T-cell mediated drug hypersensitivity syndromes. Nevirapine (NVP), is an HIV-1 antiretroviral with treatment-limiting hypersensitivity reactions (HSRs) associated with multiple class I and II HLA alleles. Here we utilize a novel analytical approach to explore these multi-allelic associations by systematically examining HLA molecules for similarities in peptide binding specificities and binding pocket structure...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819214/hiv-1-nef-induced-cardiotoxicity-through-dysregulation-of-autophagy
#3
Manish K Gupta, Rafal Kaminski, Brian Mullen, Jennifer Gordon, Tricia H Burdo, Joseph Y Cheung, Arthur M Feldman, Muniswamy Madesh, Kamel Khalili
Cardiovascular disease is a leading cause of co-morbidity in HIV-1 positive patients, even those in whom plasma virus levels are well-controlled. The pathogenic mechanism of HIV-1-associated cardiomyopathy is unknown, but has been presumed to be mediated indirectly, owing to the absence of productive HIV-1 replication in cardiomyocytes. We sought to investigate the effect of the HIV-1 auxiliary protein, Nef, which is suspected of extracellular release by infected CD4+ T cells on protein quality control and autophagy in cardiomyocytes...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817345/reverse-transcription-quantitative-polymerase-chain-reaction-for-detection-of-and-differentiation-between-rna-and-dna-of-hiv-1-based-lentiviral-vectors
#4
Melanie Pavlovic, Nina Koehler, Martina Anton, Anna Dinkelmeier, Maren Haase, Thorsten Stellberger, Ulrich Busch, Armin E Baiker
The purpose of the described method is the detection of and differentiation between RNA and DNA of human immunodeficiency virus (HIV)-derived lentiviral vectors (LV) in cell culture supernatants and swab samples. For the analytical surveillance of genetic engineering, operations methods for the detection of the HIV-1-based LV generations are required. Furthermore, for research issues, it is important to prove the absence of LV particles for downgrading experimental settings in terms of the biosafety level. Here, a quantitative polymerase chain reaction method targeting the long terminal repeat U5 subunit and the start sequence of the packaging signal ψ is described...
August 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28816644/cyp2b6-haplotype-predicts-efavirenz-plasma-concentration-in-black-south-african-hiv-1-infected-children-a-longitudinal-pediatric-pharmacogenomic-study
#5
Riaan Reay, Collet Dandara, Michelle Viljoen, Malie Rheeders
South Africa has the highest burden of the human immunodeficiency virus (HIV) infection globally. Efavirenz (EFV), a frequently used drug against HIV infection, displays a relationship between drug concentration and pharmacodynamics effects clinically. However, haplotype-based genetic variation in drug metabolism in a pediatric sample has been little considered in a longitudinal long-term context. CYP2B6 plays a key role in variation of EFV plasma concentration through altered drug metabolism. We report here on a prospective clinical pharmacogenomics/pharmacokinetic study of Bantu-speaking children, importantly, over a period of 24 months post-initiation of EFV-based treatment in South Africa...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28816583/mammalian-cell-surface-display-for-monoclonal-antibody-based-facs-selection-of-viral-envelope-proteins
#6
Tim-Henrik Bruun, Veronika Grassmann, Benjamin Zimmer, Benedikt Asbach, David Peterhoff, Alexander Kliche, Ralf Wagner
The elicitation of broadly and efficiently neutralizing antibodies in humans by active immunization is still a major obstacle in the development of vaccines against pathogens such as the human immunodeficiency virus (HIV), influenza virus, hepatitis C virus or cytomegalovirus. Here, we describe a mammalian cell surface display and monoclonal antibody (mAb)-mediated panning technology that allows affinity-based selection of envelope (Env) variants from libraries. To this end, we established an experimental setup featuring: 1) single and site specific integration of Env to link genotype and phenotype, 2) inducible Env expression to avoid cytotoxicity effects, 3) translational coupling of Env and enhanced green fluorescent protein expression to normalize for Env protein levels, and 4) display on HEK cells to ensure native folding and mammalian glycosylation...
August 17, 2017: MAbs
https://www.readbyqxmd.com/read/28816417/docking-field-based-qsar-and-pharmacophore-studies-on-the-substituted-pyrimidine-derivatives-targeting-hiv-1-reverse-transcriptase
#7
Ningning Fan, Shuang Zhang, Tao Sheng, Liang Zhao, Zhenming Liu, Junyi Liu, Xiaowei Wang
HIV-1 reverse transcriptase (RT) is one of the most important enzymes required for viral replication, thus acting as an attractive target for anti-retroviral therapy. Pyrimidine analogues reportedly have selective inhibition on HIV-1 RT with favorable antiviral activities in our previous study. To further explore the relationship between inhibitory activity and pharmacophoric characteristics, field-based QSAR models were generated and validated using Schrodinger Suite (correlation coefficient of 0.8078, cross-validated value of 0...
August 17, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28814661/hdac-inhibition-induces-hiv-1-protein-and-enables-immune-based-clearance-following-latency-reversal
#8
Guoxin Wu, Michael Swanson, Aarthi Talla, Donald Graham, Julie Strizki, Daniel Gorman, Richard Jo Barnard, Wade Blair, Ole S Søgaard, Martin Tolstrup, Lars Østergaard, Thomas A Rasmussen, Rafick-Pierre Sekaly, Nancie M Archin, David M Margolis, Daria J Hazuda, Bonnie J Howell
Promising therapeutic approaches for eradicating HIV include transcriptional activation of provirus from latently infected cells using latency-reversing agents (LRAs) and immune-mediated clearance to purge reservoirs. Accurate detection of cells capable of producing viral antigens and virions, and the measurement of clearance of infected cells, is essential to assessing therapeutic efficacy. Here, we apply enhanced methodology extending the sensitivity limits for the rapid detection of subfemtomolar HIV gag p24 capsid protein in CD4+ T cells from ART-suppressed HIV+ individuals, and we show viral protein induction following treatment with LRAs...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28814592/fever-and-generalised-lymphadenopathy-in-an-hiv-positive-patient-a-diagnostic-challenge
#9
Bernardo Neves, Pedro Raimundo, Pedro Farinha
Fever and generalised lymphadenopathy is a common presentation of a variety of diseases and a thorough investigation is often necessary for appropriate diagnosis.We present a 53-year-old male patient admitted with fever, weight loss of 15 kg in 3 months and abdominal discomfort. Examination was only remarkable for axillary and inguinal lymphadenopathy. Blood tests showed normocytic normochromic anaemia, cholestasis and a previously unknown HIV-1 infection with lymphocyte CD4 +count of 239 cells/mm(3) and viral load 3...
August 16, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28814526/hiv-1-exploits-dynamic-multi-aminoacyl-trna-synthetase-complex-to-enhance-viral-replication
#10
Alice A Duchon, Corine St-Gelais, Nathan Titkemeier, Joshua Hatterschide, Li Wu, Karin Musier-Forsyth
A hallmark of retroviruses such as human immunodeficiency virus type 1 (HIV-1) is reverse transcription of genomic RNA to DNA, a process that is primed by cellular tRNAs. HIV-1 recruits human tRNA(Lys3) to serve as the reverse transcription primer via an interaction between lysyl-tRNA synthetase (LysRS) and the HIV-1 Gag polyprotein. LysRS is normally sequestered in a multi-aminoacyl-tRNA synthetase complex (MSC). Previous studies demonstrated that components of the MSC can be mobilized in response to certain cellular stimuli, but how LysRS is redirected from the MSC to viral particles for packaging is unknown...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28814521/hiv-fusion-in-dendritic-cells-mainly-occurs-at-the-surface-and-is-limited-by-low-cd4-levels
#11
Lise Chauveau, Daniel Aaron Donahue, Blandine Monel, Francoise Porrot, Timothée Bruel, Lea Richard, Nicoletta Casartelli, Olivier Schwartz
HIV-1 poorly infects monocyte-derived dendritic cells (MDDCs). This is in a large part due to SAMHD1, which restricts viral reverse transcription. Pseudotyping HIV-1 with VSV-G strongly enhances infection, suggesting that earlier steps of viral replication, including fusion, are also inefficient in MDDCs. The site of HIV-1 fusion remains controversial and may depend on the cell type, with reports indicating that it occurs at the plasma membrane or contrarily, in an endocytic compartment. Here, we examined the pathways of HIV-1 entry in MDDCs...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28814520/contributions-of-individual-domains-to-function-of-the-hiv-1-rev-response-element
#12
Ina P O'Carroll, Yashna Thappeta, Lixin Fan, Edric A Ramirez-Valdez, Sean Smith, Yun-Xing Wang, Alan Rein
The HIV-1 Rev response element (RRE) is a 351-base element in unspliced and partially spliced viral RNA; binding of the RRE by the viral Rev protein induces nuclear export of RRE-containing RNAs, as required for virus replication. It contains one long, imperfect double helix (domain I), one branched domain (domain II) containing a high-affinity Rev-binding site, and two or three additional domains. We previously reported that the RRE assumes an "A" shape in solution and suggested that the location of the Rev binding sites in domains I and II, opposite each other on the two legs of the A, is optimal for Rev binding and explains Rev's specificity for RRE-containing RNAs...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28814519/extracellular-matrix-proteins-mediate-hiv-1-gp120-interactions-with-%C3%AE-4%C3%AE-7
#13
David Plotnik, Wenjin Guo, Brad Cleveland, Priska von Haller, Jimmy K Eng, Miklos Guttman, Kelly K Lee, James Arthos, Shiu-Lok Hu
Gut-homing α4β7(high) CD4(+) T lymphocytes have been shown to be preferentially targeted by Human Immunodeficiency Virus-1 (HIV), and are implicated in HIV pathogenesis. Previous studies demonstrated that HIV envelope protein gp120 binds and signals through α4β7, and that this likely contributes to the infection of α4β7(high) T cells and promotes cell-to-cell virus transmission. Structures within the second variable loop (V2) of gp120, including the tripeptide motif LDV/I, are thought to mediate gp120-α4β7 binding...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28814231/hiv-type-1-integrase-natural-polymorphisms-in-viral-variants-circulating-in-fsu-countries
#14
Ilya Lapovok, Vita Laga, Elena Kazennova, Marina Bobkova
BACKGROUND: Natural variability of integrase (IN) across HIV-1 variants may influence the emergence of resistant viruses. The most apparent explanation of these fact is the IN polymorphism and the associated differences in codon usage, which, in turn, influence the probability and the terms of DRMs acquisition. Possible mechanisms by which polymorphisms affect DRMs emergence remain disputed and should still be clarified because these substitutions may be associated with a reduced activity of some INSTIs and may impact on ART regimen choice depending of HIV-1 subtype...
August 15, 2017: Current HIV Research
https://www.readbyqxmd.com/read/28813503/detectable-hiv-rna-in-semen-of-hiv-controllers
#15
Marie-Laure Chaix, Faroudy Boufassa, Candice Meyzer, Marianne Leruez-Ville, Nadia Mahjoub, Marie-Laure Nere, Philippe Genet, Claudine Duvivier, Caroline Lascoux-Combes, Olivier Lambotte, Jade Ghosn
BACKGROUND: Whether spontaneous low levels of HIV-1 RNA in blood plasma correlate with low levels of HIV-1 RNA in seminal plasma has never been investigated in HIV controller (HIC) men so far. METHODS: HIC men enrolled in the ANRS CODEX cohort were eligible for the present study if they had no symptoms of sexually transmitted infections (STI). Two paired samples of blood and semen were collected four weeks apart. HIV-RNA was quantified in blood plasma (bpVL) and in seminal plasma (spVL), and cell-associated HIV-DNA was quantified in peripheral blood mononuclear cells (PBMC) and in non-sperm cells (NSC)...
2017: PloS One
https://www.readbyqxmd.com/read/28813462/a-comprehensive-profiling-of-t-and-b-lymphocyte-receptor-repertoires-from-a-chinese-origin-rhesus-macaque-by-high-throughput-sequencing
#16
Longfei Fu, Xinyang Li, Wei Zhang, Changxi Wang, Jinghua Wu, Huanming Yang, Jian Wang, Xiao Liu
Due to the close genetic background, high similarity of physiology, and susceptibility to infectious and metabolic diseases with humans, rhesus macaques have been widely used as an important animal model in biomedical research, especially in the study of vaccine development and human immune-related diseases. In recent years, high-throughput sequencing based immune repertoire sequencing (IR-SEQ) has become a powerful tool to study the dynamic adaptive immune responses. Several previous studies had analyzed the responses of B cells to HIV-1 trimer vaccine or T cell repertoire of rhesus macaques using this technique, however, there are little studies that had performed a comprehensive analysis of immune repertoire of rhesus macaques, including T and B lymphocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28812250/miv-150-and-zinc-acetate-combination-provides-potent-and-broad-activity-against-hiv-1
#17
Olga Mizenina, Mayla Hsu, Ninochka Jean-Pierre, Meropi Aravantinou, Keith Levendosky, Gabriela Paglini, Thomas M Zydowsky, Melissa Robbiani, José A Fernández-Romero
We previously showed that the combination of the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 with zinc acetate (ZA) formulated in a carrageenan (CG; MZC) gel provided macaques significant protection against vaginal simian-human immunodeficiency virus-RT (SHIV-RT) challenge, better than either MIV-150/CG or ZA/CG. The MZC gel was shown to be safe in a phase 1 clinical trial. Herein, we used in vitro approaches to study the antiviral properties of ZA and the MIV-150/ZA combination, compared to other NNRTIs...
August 15, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28811638/the-cpg-dinucleotide-content-of-the-hiv-1-envelope-gene-may-predict-disease-progression
#18
Mishi Kaushal Wasson, Jayanta Borkakoti, Amit Kumar, Banhi Biswas, Perumal Vivekanandan
The clinical course of HIV-1 varies greatly among infected individuals. Despite extensive research, virus factors associated with slow-progression remain poorly understood. Identification of unique HIV-1 genomic signatures linked to slow-progression remains elusive. We investigated CpG dinucleotide content in HIV-1 envelope gene as a potential virus factor in disease progression. We analysed 1808 HIV-1 envelope gene sequences from three independent longitudinal studies; this included 1280 sequences from twelve typical-progressors and 528 sequences from six slow-progressors...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811321/identification-of-drivers-for-the-metamorphic-transition-of-hiv-1-reverse-transcriptase
#19
Xunhai Zheng, Geoffrey A Mueller, Kyungmin Kiim, Lalith Perera, Eugene F DeRose, Robert E London
Recent structural characterizations of the p51 and p66 monomers has established an important starting point for understanding the maturation pathway of the HIV-1 reverse transcriptase p66/p51 heterodimer. This process requires a metamorphic transition of the polymerase domain leading to formation of a p66/p66' homodimer that exists as a structural heterodimer. In order to better understand the drivers for this metamorphic transition, we have performed NMR studies of (15)N-labeled RT216 - a construct that includes the fingers and most of the palm domains...
August 15, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28811070/evaluation-of-sequence-variability-in-hiv-1-gp41-c-peptide-helix-grafted-proteins
#20
Rachel L Tennyson, Susanne N Walker, Terumasa Ikeda, Reuben S Harris, Brian R McNaughton
Many therapeutically-relevant protein-protein interactions (PPIs) have been reported that feature a helix and helix-binding cleft at the interface. Given this, different approaches to disrupting such PPIs have been developed. While short peptides (<15 amino acids) typically do not fold into a stable helix, researchers have reported chemical approaches to constraining helix structure. However, these approaches rely on laborious, and often expensive, chemical synthesis and purification. Our premise is that protein-based solutions that stabilize a therapeutically-relevant helix offer a number of advantages...
August 1, 2017: Bioorganic & Medicinal Chemistry
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