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https://www.readbyqxmd.com/read/28550120/hiv-1-decreases-nrf2-are-activity-and-phagocytic-function-in-alveolar-macrophages
#1
Bashar S Staitieh, Lingmei Ding, Wendy A Neveu, Paul Spearman, David M Guidot, Xian Fan
Respiratory complications occur frequently in individuals living with human immunodeficiency-1 virus (HIV) infection, and there is evidence that HIV-related oxidative stress impairs alveolar macrophage immune function. We hypothesized that nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a master transcription factor that activates the antioxidant response element (ARE) and regulates antioxidant defenses, has an important role in alveolar macrophage (AMs) immune dysfunction in individuals with HIV infections...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28549840/phosphatidylinositol-4-5-bisphosphate-mediated-pathophysiological-effect-of-hiv-1-tat-protein
#2
REVIEW
Bruno Beaumelle, Petra Tóth, Olfat A Malak, Christophe Chopard, Gildas Loussouarn, Nicolas Vitale
Human immunodeficiency virus (HIV)-infected cells actively release the transcriptional activator (Tat) viral protein that is required for efficient HIV gene transcription. Extracellular Tat is able to enter uninfected cells. We recently reported that internalized Tat escapes endosomes to reach the cytosol and is then recruited to the plasma membrane by phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). As a consequence, Tat strongly impairs different critical cellular functions in several cell types. Here we will review recent evidences showing that Tat, by affecting the interaction of key cellular effectors with PtdIns(4,5)P2, blocks exocytosis from neuroendocrine cells, perturbs the synaptic vesicle exo-endocytosis cycle, prevents efficient phagocytosis by macrophages, and alters potassium channel activity in cardiac cells...
May 23, 2017: Biochimie
https://www.readbyqxmd.com/read/28548638/asymmetric-recognition-of-hiv-1-envelope-trimer-by-v1v2-loop-targeting-antibodies
#3
Haoqing Wang, Harry B Gristick, Louise Scharf, Anthony P West, Rachel P Galimidi, Michael S Seaman, Natalia T Freund, Michel C Nussenzweig, Pamela J Bjorkman
The HIV-1 envelope (Env) glycoprotein binds to host cell receptors to mediate membrane fusion. The prefusion Env trimer is stabilized by V1V2 loops that interact at the trimer apex. Broadly neutralizing antibodies (bNAbs) against V1V2 loops, exemplified by PG9, bind asymmetrically as a single Fab to the apex of the symmetric Env trimer using a protruding CDRH3 to penetrate the Env glycan shield. Here we characterized a distinct mode of V1V2 epitope recognition by the new bNAb BG1 in which two Fabs bind asymmetrically per Env trimer using a compact CDRH3...
May 26, 2017: ELife
https://www.readbyqxmd.com/read/28546090/safety-and-tolerability-of-long-acting-cabotegravir-injections-in-hiv-uninfected-men-eclair-a-multicentre-double-blind-randomised-placebo-controlled-phase-2a-trial
#4
Martin Markowitz, Ian Frank, Robert M Grant, Kenneth H Mayer, Richard Elion, Deborah Goldstein, Chester Fisher, Magdalena E Sobieszczyk, Joel E Gallant, Hong Van Tieu, Winkler Weinberg, David A Margolis, Krischan J Hudson, Britt S Stancil, Susan L Ford, Parul Patel, Elizabeth Gould, Alex R Rinehart, Kimberly Y Smith, William R Spreen
BACKGROUND: Cabotegravir (GSK1265744) is an HIV-1 integrase strand transfer inhibitor with potent antiviral activity and a long half-life when administered by injection that prevented simian-HIV infection upon repeat intrarectal challenge in male macaques. We aimed to assess the safety, tolerability, and pharmacokinetics of long-acting cabotegravir injections in healthy men not at high risk of HIV-1 infection. METHODS: We did this multicentre, double-blind, randomised, placebo-controlled, phase 2a trial at ten sites in the USA...
May 22, 2017: Lancet HIV
https://www.readbyqxmd.com/read/28544321/assessment-of-mode-of-delivery-and-predictors-of-emergency-caesarean-section-among-women-living-with-hiv-in-a-matched-pair-setting-with-women-from-the-general-population-in-denmark-2002-2014
#5
M Ørbaek, K Thorsteinsson, M Helleberg, E Moseholm, T L Katzenstein, M Storgaard, I S Johansen, G Pedersen, N Weis, A-M Lebech
OBJECTIVES: We aimed to assess mode of delivery and predictors of emergency caesarean section (EmCS) in women living with HIV (WLWH) in a matched-pair setting with women from the general population (WGP) in Denmark. Further, we analysed birth plan in WLWH. METHODS: All WLWH giving birth to live-born children from 2002 to 2014 were included in the study. Data were retrieved from medical records and national registries. WLWH were matched 1:5 by age, birth year, parity and ethnicity to WGP...
May 24, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28544005/hiv-1-p55-gag-protein-induces-senescence-of-human-bone-marrow-mesenchymal-stem-cells-and-reduces-their-capacity-to-support-expansion-of-hematopoietic-stem-cells-in-vitro
#6
Ya-Hong Yuan, Shan-Shan Zhao, Xiao-Li Wang, Zhi-Ping Teng, Dong-Sheng Li, Yi Zeng
Patients with human immunodeficiency virus-1 (HIV-1) infection often present with hematopoietic failure. As the important hematopoietic support cells in the bone marrow (BM), the bone marrow mesenchymal stem cells (BMSCs) can be impacted by HIV proteins that are released by infected cells within BM. In this study, we tested whether HIV protein p55-gag could induce senescence of BMSCs and reduce their capacity to support expansion of hematopoietic stem cells in vitro. BMSCs were chronically treated with p55-gag (BMSCgag ) for up to 20 days, and their proliferative activity and senescence makers were compared to nontreated cells (BMSCcon )...
May 25, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28542587/seminal-plasma-induces-inflammation-and-enhances-hiv-1-replication-in-human-cervical-tissue-explants
#7
Andrea Introini, Stéphanie Boström, Frideborg Bradley, Anna Gibbs, Axel Glaessgen, Annelie Tjernlund, Kristina Broliden
The most immediate and evident effect of mucosal exposure to semen in vivo is a local release of proinflammatory mediators accompanied by an influx of leukocytes into the female genital mucosa (FGM). The implication of such response in HIV-1 transmission has never been addressed due to limitations of currently available experimental models. Using human tissue explants from the uterine cervix, we developed a system of mucosal exposure to seminal plasma (SP) that supports HIV-1 replication. Treatment of ectocervical explants with SP resulted in the upregulation of inflammatory and growth factors, including IL-6, TNF, CCL5, CCL20, CXCL1, and CXCL8, and IL1A, CSF2, IL7, PTGS2, as evaluated by measuring protein levels in explant conditioned medium (ECM) and gene expression in tissue...
May 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542584/the-emergence-and-evolution-of-the-research-fronts-in-hiv-aids-research
#8
David Fajardo-Ortiz, Malaquias Lopez-Cervantes, Luis Duran, Michel Dumontier, Miguel Lara, Hector Ochoa, Victor M Castano
In this paper, we have identified and analyzed the emergence, structure and dynamics of the paradigmatic research fronts that established the fundamentals of the biomedical knowledge on HIV/AIDS. A search of papers with the identifiers "HIV/AIDS", "Human Immunodeficiency Virus", "HIV-1" and "Acquired Immunodeficiency Syndrome" in the Web of Science (Thomson Reuters), was carried out. A citation network of those papers was constructed. Then, a sub-network of the papers with the highest number of inter-citations (with a minimal in-degree of 28) was selected to perform a combination of network clustering and text mining to identify the paradigmatic research fronts and analyze their dynamics...
2017: PloS One
https://www.readbyqxmd.com/read/28542550/a-spatio-temporal-assessment-of-simian-human-immunodeficiency-virus-shiv-evolution-reveals-a-highly-dynamic-process-within-the-host
#9
Alison F Feder, Christopher Kline, Patricia Polacino, Mackenzie Cottrell, Angela D M Kashuba, Brandon F Keele, Shiu-Lok Hu, Dmitri A Petrov, Pleuni S Pennings, Zandrea Ambrose
The process by which drug-resistant HIV-1 arises and spreads spatially within an infected individual is poorly understood. Studies have found variable results relating how HIV-1 in the blood differs from virus sampled in tissues, offering conflicting findings about whether HIV-1 throughout the body is homogeneously distributed. However, most of these studies sample only two compartments and few have data from multiple time points. To directly measure how drug resistance spreads within a host and to assess how spatial structure impacts its emergence, we examined serial sequences from four macaques infected with RT-SHIVmne027, a simian immunodeficiency virus encoding HIV-1 reverse transcriptase (RT), and treated with RT inhibitors...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542329/novel-agoshrna-molecules-for-silencing-of-the-ccr5-co-receptor-for-hiv-1-infection
#10
Elena Herrera-Carrillo, Ben Berkhout
Allogeneic transplantation of blood stem cells from a CCR5-Δ32 homozygous donor to an HIV-infected individual, the "Berlin patient", led to a cure. Since then there has been a search for approaches that mimic this intervention in a gene therapy setting. RNA interference (RNAi) has evolved as a powerful tool to regulate gene expression in a sequence-specific manner and can be used to inactivate the CCR5 mRNA. Short hairpin RNA (shRNA) molecules can impair CCR5 expression, but these molecules may cause unintended side effects and they will not be processed in cells that lack Dicer, such as monocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28542081/dapivirine-vaginal-ring-use-does-not-diminish-the-effectiveness-of-hormonal-contraception
#11
Jennifer E Balkus, Thesla Palanee-Phillips, Krishnaveni Reddy, Samantha Siva, Ishana Harkoo, Clemensia Nakabiito, Kenneth Kintu, Gonasangrie Nair, Catherine Chappell, Flavia Matovu Kiweewa, Samuel Kabwigu, Logashvari Naidoo, Nitesha Jeenarain, Mark Marzinke, Lydia Soto-Torres, Elizabeth R Brown, Jared M Baeten
OBJECTIVE: To evaluate the potential for a clinically relevant drug-drug interaction with concomitant use of a dapivirine vaginal ring, a novel antiretroviral-based HIV-1 prevention strategy, and hormonal contraception by examining contraceptive efficacies with and without dapivirine ring use. DESIGN: A secondary analysis of women participating in MTN-020/ASPIRE, a randomized, double-blind, placebo-controlled trial of the dapivirine vaginal ring for HIV-1 prevention...
May 23, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28540990/change-in-renal-function-among-hiv-infected-koreans-receiving-tenofovir-disoproxil-fumarate-backbone-antiretroviral-therapy-a-3-year-follow-up-study
#12
Kyoung Hwa Lee, Ji Un Lee, Nam Su Ku, Su Jin Jeong, Sang Hoon Han, Jun Yong Choi, Young Goo Song, June Myung Kim
PURPOSE: Tenofovir disoproxil fumarate (TDF) is commonly prescribed as a fixed-dose, co-formulated antiretroviral drug for HIV-1 infection. The major concern of long-term TDF use is renal dysfunction. However, little is known about the long-term patterns of changes in renal function in HIV-infected Koreans receiving TDF. MATERIALS AND METHODS: We prospectively followed 50 HIV-infected Koreans, performing laboratory tests every 3 months during the first year and every 6 months for the next 2 years...
July 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28540766/hiv-1-full-genome-phylogenetics-of-generalized-epidemics-in-sub-saharan-africa-impact-of-missing-nucleotide-characters-in-next-generation-sequences
#13
Oliver Ratmann, Chris Wymant, Caroline Colijn, Siva Danaviah, M Essex, Simon D W Frost, Astrid Gall, Simani Gaiseitsiwe, Mary Grabowski, Ronald Gray, Stephane Guindon, Arndt von Haeseler, Pontiano Kaleebu, Michelle Kendall, Alexey Kozlov, Justen Manasa, Bui Quang Minh, Sikhulile Moyo, Vladimir Novitsky, Rebecca Nsubuga, Sureshnee Pillay, Thomas C Quinn, David Serwadda, Deogratius Ssemwanga, Alexandros Stamatakis, Jana Trifinopoulos, Maria Wawer, Andrew Leigh Brown, Tulio de Oliveira, Paul Kellam, Deenan Pillay, Christophe Fraser
To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the 'Phylogenetics and Networks for Generalised HIV Epidemics in Africa' consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3,985 PANGEA-HIV consensus sequences from four cohort sites (Rakai Community Cohort Study, n=2,833; MRC/UVRI Uganda, n=701; Mochudi Prevention Project, n=359; Africa Health Research Institute Resistance Cohort, n=92). Next-generation sequencing success rates varied: more than 80% of the viral genome from the gag to the nef genes could be determined for all sequences from South Africa, 75% of sequences from Mochudi, 60% of sequences from MRC/UVRI Uganda, and 22% of sequences from Rakai...
May 25, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28540745/uvaria-angolensis-as-a-promising-source-of-inhibitors-of-hiv-1-rt-associated-rna-dependent-dna-polymerase-and-rnase-h-functions
#14
Alvine Ngoutane Mfopa, Angela Corona, Kodjo Eloh, Enzo Tramontano, Aldo Frau, Fabrice Fekam Boyom, Pierluigi Caboni, Graziella Tocco
Reverse transcriptase (RT)-associated DNA polymerase (RDDP) and ribonucleaser H (RNase H) functions are both essential for HIV-1 genome replication, and the identification of new inhibitors to block both of them is a goal actively pursued by the scientific community. In this field, natural extracts have shown a great potential as source of new antivirals. In the present work, we investigated the effect of Uvaria angolensis extracts on the HIV-1 reverse transcriptase-associated DNA polymerase and ribonuclease H activities...
May 25, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28539656/pkc-%C3%AE-isoform-plays-a-crucial-role-in-tat-tlr4-signalling-pathway-to-activate-nf-%C3%AE%C2%BAb-and-cxcl8-production
#15
Manutea Serrero, Rémi Planès, Elmostafa Bahraoui
HIV-1 Tat protein induces the production of CXCL8 chemokine in a TLR4/MD2 and PKC dependent manner. The objective of this study was to understand whether these two pathways were distinct or constituted a single common pathway, and to determine the nature of the PKC isoforms involved and their interrelation with the activation of NF-κB and CXCL8 gene product expression. Here, we show that Tat-induced CXCL8 production is essentially dependent on the activation of PKC delta isoform, as shown a) by the capacity of PKC delta dominant negative (DN), and Rottlerin, a selective PKC delta pharmacological inhibitor, to inhibit Tat-induced CXCL8 production and b) by the ability of the constitutively active (CAT) isoform of PKC delta to induce CXCL8 production in a HEK cell line in the absence of Tat stimulation...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539614/the-ccr5-antagonist-maraviroc-reverses-hiv-1-latency-in-vitro-alone-or-in-combination-with-the-pkc-agonist-bryostatin-1
#16
María Rosa López-Huertas, Laura Jiménez-Tormo, Nadia Madrid-Elena, Carolina Gutiérrez, Sara Rodríguez-Mora, Mayte Coiras, José Alcamí, Santiago Moreno
A potential strategy to cure HIV-1 infection is to use latency reversing agents (LRAs) to eliminate latent reservoirs established in resting CD4+ T (rCD4+) cells. As no drug has been shown to be completely effective, finding new drugs and combinations are of increasing importance. We studied the effect of Maraviroc (MVC), a CCR5 antagonist that activates NF-κB, on HIV-1 replication from latency. HIV-1-latency models based on CCL19 or IL7 treatment, before HIV-1 infection were used. Latently infected primary rCD4+ or central memory T cells were stimulated with MVC alone or in combination with Bryostatin-1, a PKC agonist known to reverse HIV-1 latency...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539453/epigenetic-metabolite-acetate-inhibits-class-i-ii-histone-deacetylases-promotes-histone-acetylation-and-increases-hiv-1-integration-in-cd4-t-cells
#17
Jean-François Bolduc, Laurent Hany, Corinne Barat, Michel Ouellet, Michel J Tremblay
In this study, we investigated the effect of acetate, the most concentrated short-chain fatty acid (SCFA) in the gut and bloodstream, on the susceptibility of primary human CD4(+) T cells to HIV-1 infection. We report that HIV-1 replication is increased in CD3/CD28-costimulated CD4(+) T cells upon acetate treatment. This enhancing effect correlates with an increased expression of the early activation marker CD69 and impaired class I/II histone deacetylase (HDAC) activity. In addition, acetate enhances acetylation of histones H3 and H4 and augments HIV-1 integration in the genome of CD4(+) T cells...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539452/interactions-between-hiv-1-gag-and-viral-rna-genome-enhance-virion-assembly
#18
Kari A Dilley, Olga A Nikolaitchik, Andrea Galli, Ryan C Burdick, Louis Levine, Kelvin Li, Alan Rein, Vinay K Pathak, Wei-Shau Hu
Most HIV-1 virions contain two copies of full-length viral RNA, indicating that genome packaging is efficient and tightly regulated. However, the structural protein Gag is the only component required for the assembly of noninfectious virus-like particles and the viral RNA is dispensable in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle production when Gag is expressed at levels similar to those in cells containing one provirus...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539451/reducing-v3-antigenicity-and-immunogenicity-on-soluble-native-like-hiv-1-env-sosip-trimers
#19
Rajesh P Ringe, Gabriel Ozorowski, Kimmo Rantalainen, Weston B Struwe, Katie Matthews, Jonathan L Torres, Anila Yasmeen, Christopher A Cottrell, Thomas J Ketas, Celia C LaBranche, David C Montefiori, Albert Cupo, Max Crispin, Ian A Wilson, Andrew B Ward, Rogier W Sanders, P J Klasse, John P Moore
Native-like trimers of the SOSIP design are being developed as immunogens in human immunodeficiency virus type 1 (HIV-1) vaccine development programs. These trimers display the epitopes for multiple broadly neutralizing antibodies (bNAbs), but can also expose binding sites for some types of non-neutralizing antibodies (non-NAbs). Among the latter are epitopes in the gp120 V3 region that are highly immunogenic when SOSIP trimers are evaluated in animal models. It is presently uncertain whether antibodies against V3 can interfere with the induction of NAbs, but there are good arguments in favor of suppressing such "off-target" immune responses...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539449/anti-hiv-1-adcc-antibodies-following-latency-reversal-and-treatment-interruption
#20
Wen Shi Lee, Anne B Kristensen, Thomas A Rasmussen, Martin Tolstrup, Lars Østergaard, Ole S Søgaard, Bruce D Wines, P Mark Hogarth, Arnold Reynaldi, Miles P Davenport, Sean Emery, Janaki Amin, David A Cooper, Virginia L Kan, Julie Fox, Henning Gruell, Matthew S Parsons, Stephen J Kent
There is growing interest in utilizing antibody-dependent cellular cytotoxicity (ADCC) to eliminate infected cells following reactivation from HIV-1 latency. A potential barrier is that HIV-1-specific ADCC antibodies decline in patients on long-term antiretroviral therapy (ART) and may not be sufficient to eliminate reactivated latently infected cells. It is not known whether reactivation from latency with latency-reversing agents (LRA) could provide sufficient antigenic stimulus to boost HIV-1-specific ADCC...
May 24, 2017: Journal of Virology
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