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https://www.readbyqxmd.com/read/28646196/nucleoside-reverse-transcriptase-inhibitors-nrtis-induce-proinflammatory-cytokines-in-the-cns-via-wnt5a-signaling
#1
Ting Wu, Juan Zhang, Mingxing Geng, Shao-Jun Tang, Wenping Zhang, Jianhong Shu
HAART is very effective in suppressing HIV-1 replication in patients. However, patients staying on long-term HAART still develop various HIV-associated neurological disorders, even when the viral load is low. The underlying pathogenic mechanisms are largely unknown. Emerging evidence implicated that persistent neuroinflammation plays an important role in NeuroAIDS. Although residual virus or viral proteins are commonly thought as the causal factors, we are interested in the alternative possibility that HAART critically contributes to the neuroinflammation in the central nervous system (CNS)...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645727/inhibition-of-non-canonical-hiv-1-tat-secretion-through-the-cellular-na-k-atpase-blocks-hiv-1-infection
#2
Silvia Agostini, Hashim Ali, Chiara Vardabasso, Antonio Fittipaldi, Ennio Tasciotti, Anna Cereseto, Antonella Bugatti, Marco Rusnati, Marina Lusic, Mauro Giacca
Besides its essential role in the activation of HIV-1 gene expression, the viral Tat protein has the unusual property of trafficking in and out of cells. In contrast to Tat internalization, the mechanism involved in extracellular Tat release has so far remained elusive. Here we show that Tat secretion occurs through a Golgi-independent pathway requiring binding of Tat with three short, non-consecutive intracytoplasmic loops at the C-terminus of the cellular Na(+),K(+)-ATPase pump alpha subunit. Ouabain, a pump inhibitor, blocked this interaction and prevented Tat secretion; virions produced in the presence of this drug were less infectious, consistent the capacity of virion-associated Tat to increase HIV-1 infectivity...
June 13, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28645708/identification-of-major-routes-of-hiv-transmission-throughout-mesoamerica
#3
Antoine Chaillon, Santiago Avila-Ríos, Joel O Wertheim, Ann Dennis, Claudia García-Morales, Daniela Tapia-Trejo, Carlos Mejía-Villatoro, Juan M Pascale, Guillermo Porras-Cortés, Carlos J Quant-Durán, Ivette Lorenzana, Rita I Meza, Elsa Y Palou, Marvin Manzanero, Rolando A Cedillos, Gustavo Reyes-Terán, Sanjay R Mehta
BACKGROUND: Migration and travel are major drivers of the spread of infectious diseases. Geographic proximity and a common language facilitate travel and migration in Mesoamerica, which in turn could affect the spread of HIV in the region. METHODS: 6092 HIV-1 subtype B partial pol sequences sampled from unique antiretroviral treatment-naïve individuals from Mexico (40.7%), Guatemala (24.4%), Honduras (19%), Panama (8.2%), Nicaragua (5.5%), Belize (1.4%), and El Salvador (0...
June 20, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28645240/engineered-expression-of-broadly-neutralizing-antibodies-against-human-immunodeficiency-virus
#4
Maham Ahmad, Osama M Ahmed, Bruce Schnepp, Philip R Johnson
This review discusses recent progress made in developing a vaccine and novel treatments for human immunodeficiency virus (HIV). It highlights the shortcomings of the RV144 vaccination trial [ALVAC-HIV (vCP1521) and AIDSVAX B/E] and the current standard of care and proposes that engineered expression of broadly neutralizing antibodies (bNAbs) against HIV-1 could overcome these shortcomings. Current developments in three major lines of research on HIV prevention and treatment using bNAbs are reviewed: firstly, the use of sequential immunogens to activate B cells to express bNAbs; secondly, the delivery of novel and extremely potent bNAbs through passive administration; and finally, the use of gene transfer using adeno-associated viral vectors to deliver bNAbs...
June 23, 2017: Annual Review of Virology
https://www.readbyqxmd.com/read/28645207/development-and-validation-of-an-electronic-medical-record-emr-based-computed-phenotype-of-hiv-1-infection
#5
Devon W Paul, Nigel B Neely, Meredith Clement, Isaretta Riley, Mashael Al-Hegelan, Matthew Phelan, Monica Kraft, David M Murdoch, Joseph Lucas, John Bartlett, Mehri McKellar, Loretta G Que
Background: Electronic medical record (EMR) computed algorithms allow investigators to screen thousands of patient records to identify specific disease cases. No computed algorithms have been developed to detect all cases of human immunodeficiency virus (HIV) infection using administrative, laboratory, and clinical documentation data outside of the Veterans Health Administration. We developed novel EMR-based algorithms for HIV detection and validated them in a cohort of subjects in the Duke University Health System (DUHS)...
June 22, 2017: Journal of the American Medical Informatics Association: JAMIA
https://www.readbyqxmd.com/read/28645089/drug-resistance-mechanism-of-l10f-l10f-n88s-and-l90m-mutations-in-crf01_ae-hiv-1-protease-molecular-dynamics-simulations-and-binding-free-energy-calculations
#6
C S Vasavi, Ramasamy Tamizhselvi, Punnagai Munusami
HIV-1 protease plays a crucial role in viral replication and maturation, which makes it one of the most attractive targets for anti-retroviral therapy. The majority of HIV infections in developing countries are due to non-B subtype. Subtype AE is spreading rapidly and infecting huge population worldwide. The mutations in the active site of subtype AE directly impair the interactions with the inhibitor. The non-active site mutations influence the binding of the inhibitor indirectly and their resistance mechanism is not well understood...
June 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28642743/hiv-1-nef-signaling-in-intestinal-mucosa-epithelium-suggests-the-existence-of-an-active-inter-kingdom-crosstalk-mediated-by-exosomes
#7
REVIEW
Cristina Felli, Olimpia Vincentini, Marco Silano, Andrea Masotti
The human intestinal mucosal surface represents the first defense against pathogens and regulates the immune response through the combination of epithelial cell (EC) functions and immunological factors. ECs act as sensors of luminal stimuli and interact with the immune cells through signal-transduction pathways, thus representing the first barrier that HIV-1 virus encounters during infection. In particular, the HIV-1 Nef protein plays a crucial role in viral invasion and replication. Nef is expressed early during viral infection and interacts with numerous cellular proteins as a scaffold/adaptor...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28642469/tracing-the-epidemic-history-of-hiv-1-crf01_ae-clusters-using-near-complete-genome-sequences
#8
Xingguang Li, Haizhou Liu, Lu Liu, Yi Feng, Marcia L Kalish, Simon Y W Ho, Yiming Shao
Human immunodeficiency virus (HIV) has a number of circulating recombinant forms that are the product of recombination between different HIV subtypes. The first circulating recombinant form of HIV-1 to be identified was CRF01_AE, which originated in Central Africa and is now most prevalent in Southeast and East Asia. In this study, we investigated the timescale, evolutionary history, and population genetics of the HIV-1 CRF01_AE strains primarily responsible for the epidemic in Asia. A further aim of our study was to define and standardize the nomenclature and provide well-characterized reference sequences for the phylogenetic transmission clusters of CRF01_AE...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28641798/hiv-1-associated-atherosclerosis-unraveling-the-missing-link
#9
REVIEW
Alison Kearns, Jennifer Gordon, Tricia H Burdo, Xuebin Qin
Cardiovascular disease, including atherosclerosis and atherosclerosis-associated complications, is an increasing cause of morbidity and mortality in human immunodeficiency virus (HIV) patients in the post-antiretroviral therapy era. HIV alone accelerates atherosclerosis. Antiretroviral therapy; HIV-associated comorbidities, such as dyslipidemia, drug abuse, and opportunistic infections; and lifestyle are risk factors for HIV-associated atherosclerosis. However, our current understanding of HIV-associated atherogenesis is very limited and has largely been obtained from clinical observation...
June 27, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28641539/role-of-host-factors-on-the-regulation-of-tat-mediated-hiv-1-transcription
#10
Guillaume Mousseau, Susana T Valente
BACKGROUND: The viral transactivator Tat protein is a key modulator of HIV-1 replication, as it regulates transcriptional elongation from the integrated proviral genome. Tat recruits the human transcription elongation factor b, and other host proteins, such as the super elongation complex, to activate the cellular RNA polymerase II, normally stalled shortly after transcription initiation at the HIV promoter. By means of a complex set of interactions with host cellular factors, Tat determines the fate of viral activity within the infected cell...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641535/hiv-1-transcription-inhibitors-increase-the-synthesis-of-viral-non-coding-rna-that-contribute-to-latency
#11
Yao A Akpamagbo, Catherine DeMarino, Michelle L Pleet, Angela Schwab, Myosotys Rodriguez, Robert A Barclay, Gavin Sampey, Sergey Iordanskiy, Nazira El-Hage, Fatah Kashanchi
BACKGROUND: HIV-1 can be preserved in long-lived resting CD4+ T- and myeloid cells, forming a viral reservoir in tissues of the infected individuals. Infected patients primarily receive cART, which, to date, is the most efficient treatment against HIV/AIDS. However, the major problem in the eradication of HIV-1 from patients is the lack of therapeutic approaches to recognize the latent HIV-1 provirus and to eliminate latently infected cells. RESULTS: In the current review, we describe the effect of HIV-1 transcriptional inhibitors CR8#13 and F07#13 using a series of in vitro and in vivo assays...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641512/molecular-docking-and-molecular-dynamics-simulation-based-approach-to-explore-the-dual-inhibitor-against-hiv-1-reverse-transcriptase-and-integrase
#12
Subhash Chander, Rajan Kumar Pandey, Ashok Penta, Bhanwar Singh Choudhary, Manish Sharma, Ruchi Malik, Vijay Kumar Prajapati, Sankaranarayanan Murugesan
HIV integrase (IN) and reverse transcriptase (RT) are key enzymes for the replication of HIV-1. DNA polymerase and ribonuclease H (RNase H) are the two catalytic domains of HIV-1 RT which are validated as drug targets because of their essence for replication. IN and RNase H domain of RT share the striking structural similarity; it contains conserved DDE triad (two aspartates and one glutamate) and a pair of divalent Mg2+/Mn2+ ions at their catalytic core domain. Therefore, the search of compounds with dual inhibition of IN and RNase H can be the viable and more efficacious approach for the drug development against both wild and drug resistance strains of HIV...
June 15, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28639993/peripheral-monocytes-macrophages-phenotypes-associated-to-the-evolution-of-cognitive-performance-in-hiv-infected-patients
#13
Massimiliano Fabbiani, Antonio Muscatello, Paolo Perseghin, Marco Bani, Arianna Incontri, Nicola Squillace, Giuseppe Lapadula, Andrea Gori, Alessandra Bandera
BACKGROUND: The contribution of monocyte activation in the development of HIV-associated neurocognitive disorders is not completely understood. This study aimed to explore the predictive value of peripheral monocyte/macrophage (M/M) phenotypes on the evolution of cognitive performance in a population of virologically-suppressed HIV-infected patients. SETTING: Prospective, observational, longitudinal study. METHODS: HIV-1-infected patients with HIV-RNA<50copies/mL for >12 months underwent neuropsychological examination at baseline and after one year...
June 19, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28639219/signature-pattern-analysis-for-the-full-length-env-gene-of-the-earliest-korean-subclade-b-of-hiv-1-outbreak-among-korean-hemophiliacs
#14
Young-Keol Cho, Jung-Eun Kim, Daeun Jeong, Brian T Foley
The epidemiological link in the hypervariable env gene between viruses infecting HIV-positive hemophiliacs (HPs) and plasma donors was not studied. We determined full-length env gene sequences in 20 HPs, 3 plasma donors whose plasma was used for domestic clotting factor (DCF) production, and 54 local controls (LCs). Env genes from viruses in frozen stored sera obtained 1-3 years after diagnosis and from samples collected several years after infection were amplified via RT-PCR and subjected to direct sequencing...
June 21, 2017: Virus Genes
https://www.readbyqxmd.com/read/28639194/rnaa-induced-by-tata-box-targeting-micrornas
#15
Yijun Zhang, Hui Zhang
Recent studies reveal that some nuclear microRNAs (miRNA) and synthesized siRNAs target gene promoters to activate gene transcription (RNAa). Interestingly, our group identified a novel HIV-1-encoded miRNA, miR-H3, which targets specifically the core promoter TATA box of HIV-1 and activates viral gene expression. Depletion of miR-H3 significantly impaired the replication of HIV-1. miR-H3 mimics could activate viruses from CD4(+) T cells isolated from patients receiving suppressive highly active antiretroviral therapy, which is very intriguing for reducing HIV-1 latent reservoir...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28638661/efficacy-and-tolerability-of-tenofovir-disoproxil-fumarate-based-regimen-as-compared-to-zidovudine-based-regimens-a-systematic-review-and-meta-analysis
#16
REVIEW
Tegene Legese Dadi, Adane Teshome Kefale, Teshale Ayele Mega, Muktar Sano Kedir, Habtamu Acho Addo, Tessema Tsehay Biru
BACKGROUND: Although tenofovir (TDF)/emtricitabine (FTC)/efavirenz (EFV) and zidovudine (ZDV)/lamivudine (3TC)/efavirenz (EFV) are used as preferred first line regimen, their head-to-head comparison in terms of their efficacy and tolerability was limited. This review aimed to synthesize the best available evidence on the comparative efficacy and tolerability of the two regimens. METHODS: Seven sites and databases in addition to Google search until August 20, 2016, were searched...
2017: AIDS Research and Treatment
https://www.readbyqxmd.com/read/28638377/a-novel-bromodomain-inhibitor-reverses-hiv-1-latency-through-specific-binding-with-brd4-to-promote-tat-and-p-tefb-association
#17
Huachao Huang, Shuai Liu, Maxime Jean, Sydney Simpson, He Huang, Mark Merkley, Tsuyoshi Hayashi, Weili Kong, Irene Rodríguez-Sánchez, Xiaofeng Zhang, Hailemichael O Yosief, Hongyu Miao, Jianwen Que, James J Kobie, James Bradner, Netty G Santoso, Wei Zhang, Jian Zhu
While combinatory antiretroviral therapy (cART) can effectively reduce HIV-1 viremia, it cannot eliminate HIV-1 infection. In the presence of cART, viral reservoirs remain latent, impeding the cure of HIV-1/AIDS. Recently, latency-reversing agents (LRAs) have been developed with the intent of purging latent HIV-1, providing an intriguing strategy for the eradication of the residual viral reservoirs. Our earlier studies show that the first-generation, methyl-triazolo bromodomain, and extra-terminal domain inhibitor (BETi), JQ1, facilitates the reversal of HIV-1 latency...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28638104/anti-proliferative-therapy-for-hiv-cure-a-compound-interest-approach
#18
Daniel B Reeves, Elizabeth R Duke, Sean M Hughes, Martin Prlic, Florian Hladik, Joshua T Schiffer
In the era of antiretroviral therapy (ART), HIV-1 infection is no longer tantamount to early death. Yet the benefits of treatment are available only to those who can access, afford, and tolerate taking daily pills. True cure is challenged by HIV latency, the ability of chromosomally integrated virus to persist within memory CD4(+) T cells in a non-replicative state and activate when ART is discontinued. Using a mathematical model of HIV dynamics, we demonstrate that treatment strategies offering modest but continual enhancement of reservoir clearance rates result in faster cure than abrupt, one-time reductions in reservoir size...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637761/mother-to-child-hiv-transmission-bottleneck-selects-for-consensus-virus-with-lower-gag-protease-driven-replication-capacity
#19
Vanessa L Naidoo, Jaclyn K Mann, Christie Noble, Emily Adland, Jonathan M Carlson, Jake Thomas, Chanson J Brumme, Christina F Thobakgale-Tshabalala, Zabrina L Brumme, Mark A Brockman, Philip J R Goulder, Thumbi Ndung'u
HIV infection is in the large majority of cases established by a single variant and understanding the characteristics of successfully transmitted variants is relevant to prevention strategies. Few studies have investigated the viral determinants of mother-to-child transmission. To determine the impact of Gag-protease driven viral replication capacity on mother-to-child transmission, the replication capacities of 148 recombinant viruses encoding plasma derived Gag-protease from 53 non-transmitter mothers, 48 transmitter mothers and 47 infected infants were assayed in an HIV-1 inducible green fluorescent protein reporter cell line...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28637198/multi-target-activity-of-hemidesmus-indicus-decoction-against-innovative-hiv-1-drug-targets-and-characterization-of-lupeol-mode-of-action
#20
Francesca Esposito, Manuela Mandrone, Claudia Del Vecchio, Ilaria Carli, Simona Distinto, Angela Corona, Mariacaterina Lianza, Dario Piano, Massimo Tacchini, Elias Maccioni, Filippo Cottiglia, Elisa Saccon, Ferruccio Poli, Cristina Parolin, Enzo Tramontano
Despite the availability of several anti-retrovirals there is still an urgent need for developing novel therapeutic strategies and finding new drugs against underexplored HIV-1 targets. Among them, there are the HIV-1 Reverse Transcriptase (RT)-associated Ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum. It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors...
June 20, 2017: Pathogens and Disease
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