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https://www.readbyqxmd.com/read/29785023/hiv-vaccine-candidate-activation-of-hypoxia-and-the-inflammasome-in-cd14-monocytes-is-associated-with-a-decreased-risk-of-siv-mac251-acquisition
#1
Monica Vaccari, Slim Fourati, Shari N Gordon, Dallas R Brown, Massimilano Bissa, Luca Schifanella, Isabela Silva de Castro, Melvin N Doster, Veronica Galli, Maria Omsland, Dai Fujikawa, Giacomo Gorini, Namal P M Liyanage, Hung V Trinh, Katherine M McKinnon, Kathryn E Foulds, Brandon F Keele, Mario Roederer, Richard A Koup, Xiaoying Shen, Georgia D Tomaras, Marcus P Wong, Karissa J Munoz, Johannes S Gach, Donald N Forthal, David C Montefiori, David J Venzon, Barbara K Felber, Margherita Rosati, George N Pavlakis, Mangala Rao, Rafick-Pierre Sekaly, Genoveffa Franchini
Qualitative differences in the innate and adaptive responses elicited by different HIV vaccine candidates have not been thoroughly investigated. We tested the ability of the Aventis Pasteur live recombinant canarypox vector (ALVAC)-SIV, DNA-SIV and Ad26-SIV vaccine prime modalities together with two ALVAC-SIV + gp120 protein boosts to reduce the risk of SIVmac251 acquisition in rhesus macaques. We found that the DNA and ALVAC prime regimens were effective, but the Ad26 prime was not. The activation of hypoxia and the inflammasome in CD14+ CD16- monocytes, gut-homing CCR5-negative CD4+ T helper 2 (TH 2) cells and antibodies to variable region 2 correlated with a decreased risk of SIVmac251 acquisition...
May 21, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29781885/improved-cognitive-performance-and-reduced-monocyte-activation-in-virally-suppressed-chronic-hiv-following-dual-ccr2-and-ccr5-antagonism
#2
Michelle L D'Antoni, Robert H Paul, Brooks I Mitchell, Lindsay Kohorn, Laurent Fischer, Eric Lefebvre, Star Seyedkazemi, Beau K Nakamoto, Maegen Walker, Kalpana J Kallianpur, Debra Ogata-Arakaki, Lishomwa C Ndhlovu, Cecilia Shikuma
OBJECTIVE: To evaluate changes in neuropsychological (NP) performance and in plasma and cell surface markers of peripheral monocyte activation/migration following treatment with cenicriviroc (CVC), a dual C-C chemokine receptor type 2 (CCR2) and type 5 (CCR5) antagonist, in treatment-experienced, HIV-infected individuals. SETTING: Single-arm, 24-week, open-label clinical trial. METHODS: HIV-infected individuals on antiretroviral therapy (ART) >1 year with plasma HIV RNA <50 copies/ml and below-normal cognitive performance [defined as age, gender and education-adjusted NP performance (NPZ) <-0...
May 16, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29772686/inhibition-of-the-ccl5-ccr5-axis-against-the-progression-of-gastric-cancer
#3
REVIEW
Donatella Aldinucci, Naike Casagrande
Despite the progress made in molecular and clinical research, patients with advanced-stage gastric cancer (GC) have a bad prognosis and very low survival rates. Furthermore, it is challenging to find the complex molecular mechanisms that are involved in the development of GC, its progression, and its resistance to therapy. The interactions of chemokines, also known as chemotactic cytokines, with their receptors regulate immune and inflammatory responses. However, updated research demonstrates that cancer cells subvert the normal chemokine role, transforming them into fundamental constituents of the tumor microenvironment (TME) with tumor-promoting effects...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772059/the-orphan-g-protein-coupled-receptor-75-signaling-is-activated-by-the-chemokine-ccl5
#4
Simona Dedoni, Lee A Campbell, Brandon K Harvey, Valeria Avdoshina, Italo Mocchetti
The chemokine CCL5 prevents neuronal cell death mediated both by amyloid β, as well as the human immunodeficiency virus (HIV) viral proteins gp120 and Tat. Because CCL5 binds to CCR5, CCR3 and/or CCR1 receptors, it is unclear which of these receptors plays a role in neuroprotection. Indeed, CCL5 also has neuroprotective activity in cells lacking these receptors. CCL5 may bind to a G protein-coupled receptor 75 (GPR75), which encodes for a 540 amino-acid orphan receptor of the Gqα family. In this study, we have used SH-SY5Y human neuroblastoma cells to characterize whether CCL5 could activate a Gq signaling through GPR75...
May 17, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29767965/bifunctional-chimera-that-coordinately-targets-human-immunodeficiency-virus-1-hiv-1-envelope-gp120-and-host-cell-ccr5-co-receptor-at-the-virus-cell-interface
#5
Adel A Rashad, Li-Rui Song, Andrew P Holmes, Kriti Acharya, Shiyu Zhang, Zhi-Long Wang, Ebony Gary, Xin Xie, Vanessa Pirrone, Michele A Kutzler, Ya-Qiu Long, Irwin Chaiken
To address the urgent need for new agents to reduce the global occurrence and spread of AIDS, we investigated the underlying hypothesis that antagonists of HIV-1 Envelope (Env) gp120 and host cell co-receptor (CoR) proteins can be covalently joined into bifunctional synergistic combinations that will improve antiviral. A synthetic protocol was established to covalently combine a CCR5 small molecule antagonist and a gp120 peptide triazole antagonist to form the bifunctional chimera. Importantly, the chimeric inhibitor preserved the specific targeting properties of the two separate chimera components, and at the same time exhibited low to sub-nanomolar potencies, in inhibiting cell infection by different pseudoviruses, that were substantially greater than those of a non-covalent mixture of individual components...
May 16, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29766813/coreceptor-tropism-and-maraviroc-sensitivity-of-clonally-derived-ethiopian-hiv-1c-strains-using-an-in-house-phenotypic-assay-and-commonly-used-genotypic-methods
#6
Amare Worku Kalu, Nigus Fikrie Telele, Shambhu Aralaguppe, Solomon Gebre-Selassie, Daniel Fekade, Gaetano Marrone, Anders Sonnerborg
OBJECTIVES: Genotypic tropism testing (GTT) tools are generally developed based on HIV-1 subtype B (HIV-1B) and used for HIV-1C as well but with a large discordance of prediction between different methods. We used an established phenotypic assay for comparison with GTT methods and for determination of in vitro maraviroc sensitivity of pure R5-tropic and dual-tropic HIV-1C. METHODS: Plasma was obtained from 58 HIV-1C infected Ethiopians. Envgp120 was cloned into a luciferase tagged NL4-3 plasmid...
May 15, 2018: Current HIV Research
https://www.readbyqxmd.com/read/29762163/transcriptional-gene-silencing-limits-cxcr4-associated-depletion-of-bone-marrow-cd34-cells-in-hiv-1-infection
#7
Tetsuo Tsukamoto
OBJECTIVES: Hematological abnormalities that include changes in bone marrow, such as in anemia and pancytopenia, are common among human immunodeficiency virus (HIV)-infected patients, particularly in the advanced stage of disease. Such abnormalities may be caused by a reduced bone marrow function for hematopoiesis. This aim of this study was to determine whether transcriptional gene silence can help to preserve the hosts' hematopoietic potential in addition to peripheral CD4 T cells against CCR5-tropic HIV infection...
May 11, 2018: AIDS
https://www.readbyqxmd.com/read/29761933/th1-th17-th22-immune-response-and-their-association-with-joint-pain-imagenological-bone-loss-rankl-expression-and-osteoclast-activity-in-temporomandibular-joint-osteoarthritis-a-preliminary-report
#8
Gustavo Monasterio, Francisca Castillo, Leticia Rojas, Emilio A Cafferata, Carla Alvarez, Paola Carvajal, Cristián Núñez, Guillermo Flores, Walter Díaz, Rolando Vernal
It is well accepted that the presence of cytokines belonging to the Th1/Th17/Th22 axis of immuno-inflammatory response in the joint environment, such as IL-1β, IL-17, and IL-22, respectively, are associated with pathogenesis of several synovial joint degenerative disorders. During temporomandibular joint osteoarthritis (TMJ-OA), IL-1β and IL-17 have been implicated in the inflammation and resorption of sub-chondral bone; however, the role of Th22-response in the TMJ-OA pathophysiology has not been established...
May 15, 2018: Journal of Oral Rehabilitation
https://www.readbyqxmd.com/read/29760499/hepatic-stellate-cells-secrete-ccl5-to-induce-hepatocyte-steatosis
#9
Byeong-Moo Kim, Ahmed Maher Abdelfattah, Robin Vasan, Bryan C Fuchs, Michael Y Choi
Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of disease severity, starting from pure steatosis, leading to fatty inflammation labeled as non-alcoholic steatohepatitis (NASH), and finally fibrosis leading to cirrhosis. Activated hepatic stellate cells (HSCs) are known to contribute to fibrosis, but less is known about their function during NAFLD's early stages prior to fibrosis. We developed an ex vivo assay that cocultures primary HSCs from mouse models of liver disease with healthy hepatocytes to study their interaction...
May 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29739880/ccr5-adopts-three-homodimeric-conformations-that-control-cell-surface-delivery
#10
Jun Jin, Fanny Momboisse, Gaelle Boncompain, Florian Koensgen, Zhicheng Zhou, Nelia Cordeiro, Fernando Arenzana-Seisdedos, Franck Perez, Bernard Lagane, Esther Kellenberger, Anne Brelot
Biophysical methods and x-ray crystallography have revealed that class A G protein-coupled receptors (GPCRs) can form homodimers. We combined computational approaches with receptor cross-linking, energy transfer, and a newly developed functional export assay to characterize the residues involved in the dimerization interfaces of the chemokine receptor CCR5, the major co-receptor for HIV-1 entry into cells. We provide evidence of three distinct CCR5 dimeric organizations, involving residues of transmembrane helix 5...
May 8, 2018: Science Signaling
https://www.readbyqxmd.com/read/29739756/alternatively-activated-macrophages-upregulate-mesothelial-expression-of-p-selectin-to-enhance-adhesion-of-ovarian-cancer-cells
#11
Molly J Carroll, Kaitlin C Fogg, Harin A Patel, Harris B Krause, Anne-Sophie Mancha, Manish S Patankar, Paul S Weisman, Lisa Barroilhet, Pamela K Kreeger
Peritoneal metastasis of high-grade serous ovarian cancer (HGSOC) occurs when tumor cells suspended in ascites adhere to mesothelial cells. Despite the strong relationship between metastatic burden and prognosis in HGSOC, there are currently no therapies specifically targeting the metastatic process. We utilized a co-culture model and multivariate analysis to examine how interactions between tumor cells, mesothelial cells, and alternatively-activated macrophages (AAMs) influence the adhesion of tumor cells to mesothelial cells...
May 8, 2018: Cancer Research
https://www.readbyqxmd.com/read/29729320/ccr5%C3%AE-32-a-piece-of-protection-in-the-inflammatory-puzzle-of-multiple-sclerosis-susceptibility
#12
Lian Lopes Troncoso, Alessandra Pontillo, Enedina Maria Lobato de Oliveira, Alessandro Finkelszteijn, Silvete Schneider, José Artur Bogo Chies
BACKGROUND: Leucocyte infiltration and activation in the central nervous system (CNS) is an important step in the pathogenesis of multiple sclerosis (MS). The Chemokine receptor 5 (CCR5) is implicated in immune cell migration and cytokine release in the CNS, and it was demonstrated to strongly contribute to CNS inflammation and damage in several models of sterile and pathogen-mediated CNS diseases. Although the inhibition of CCR5 results in a beneficial effect in experimental models of MS, conflicting results have been found about the loss-of-function variant CCR5Δ32 (rs333) in MS patients...
May 2, 2018: Human Immunology
https://www.readbyqxmd.com/read/29729309/hiv-glycoprotein-gp120-enhances-mesenchymal-stem-cell-migration-by-upregulating-cxcr4-expression
#13
Lei Li, Ryan Z L Lim, Lawrence S U Lee, Nicholas S Y Chew
BACKGROUND: HIV infection and/or the direct pathogenic effects of circulating HIV proteins impairs the physiological function of mesenchymal stem cells (MSCs), and contribute to the pathogenesis of age-related clinical comorbidities in people living with HIV. The SDF-1/CXCR4 pathway is vital for modulating MSC proliferation, migration and differentiation. HIV glycoprotein gp120 inhibits SDF-1 induced chemotaxis by downregulating the expression and function of CXCR4 in monocytes, B and T cells...
May 2, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29728699/circulating-monocyte-subsets-in-human-chronic-graft-versus-host-disease
#14
Takaaki Konuma, Chisato Kohara, Eri Watanabe, Motoko Mizukami, Etsuko Nagai, Maki Oiwa-Monna, Susumu Tanoue, Masamichi Isobe, Koji Jimbo, Seiko Kato, Satoshi Takahashi, Arinobu Tojo
Chronic graft-versus-host disease (cGVHD) is a major cause of late morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Monocytes/macrophages play a central role in inflammation, tissue repair, and fibrosis, which are the main clinical features of cGVHD. Here, we examined the expression levels of activation markers, chemokine receptors, and scavenger receptors for each circulating monocyte subset in 145 patients without disease recurrence at least 12 months after undergoing allogeneic HCT...
May 4, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29724116/identification-of-a-novel-hiv-1-b-c-crf01_ae-recombinant-isolate-in-guangxi-china
#15
Chen Wang, Yan Wang, Desheng Kong, Shujia Liang, Yi Feng, Liying Ma
Continual generation of HIV-1 recombinant forms might contribute to its genetic diversity. In this study, a novel B/C/CRF01_AE recombinant virus (GX2016EU13) was identified, which was isolated from a HIV-positive man who infected through heterosexual sex in Guangxi, China. GX2016EU13 was identified as CCR5-tropic. As shown in the near full-length genome analyses, five recombinant breakpoints were found only in the pol gene of GX2016EU13, which divided the NFLG into three subtype B segments, two subtype C segments and one CRF01_AE segment...
May 4, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29723162/hiv-1-replicates-and-persists-in-vaginal-epithelial-dendritic-cells
#16
Victor Pena-Cruz, Luis M Agosto, Hisashi Akiyama, Alex Olson, Yvetane Moreau, Jean-Robert Larrieux, Andrew Henderson, Suryaram Gummuluru, Manish Sagar
HIV-1 acquisition occurs most commonly after sexual contact. To establish infection, HIV-1 must infect cells that support high level replication, namely CD4+ T cells, which are absent from the outermost genital epithelium. Dendritic cells (DCs), present in mucosal epithelia, potentially facilitate HIV-1 acquisition. We show that vaginal epithelial DCs, termed CD1a+ VEDCs, are unlike other blood and tissue derived DCs because they express langerin but not DC-SIGN, and unlike skin-based langerin+ DC subset, Langerhans cells (LC), they do not harbor Birbeck granules...
May 3, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29720426/microrna-155-modulates-acute-graft-versus-host-disease-by-impacting-t-cell-expansion-migration-and-effector-function
#17
Nina C Zitzer, Katiri Snyder, Xiamoei Meng, Patricia A Taylor, Yvonne A Efebera, Steven M Devine, Bruce R Blazar, Ramiro Garzon, Parvathi Ranganathan
MicroRNA-155 (miR-155) is a small noncoding RNA critical for the regulation of inflammation as well as innate and adaptive immune responses. MiR-155 has been shown to be dysregulated in both donor and recipient immune cells during acute graft-versus-host disease (aGVHD). We previously reported that miR-155 is upregulated in donor T cells of mice and humans with aGVHD and that mice receiving miR-155-deficient (miR155-/- ) splenocytes had markedly reduced aGVHD. However, molecular mechanisms by which miR-155 modulates T cell function in aGVHD have not been fully investigated...
May 2, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29719539/natural-killer-cell-recruitment-to-the-lung-during-influenza-a-virus-infection-is-dependent-on-cxcr3-ccr5-and-virus-exposure-dose
#18
Lindsey E Carlin, Emily A Hemann, Zeb R Zacharias, Jonathan W Heusel, Kevin L Legge
Natural killer (NK) cells are vital components of the antiviral immune response, but their contributions in defense against influenza A virus (IAV) are not well understood. To better understand NK cell responses during IAV infections, we examined the magnitude, kinetics, and contribution of NK cells to immunity and protection during high- and low-dose IAV infections. Herein, we demonstrate an increased accumulation of NK cells in the lung in high-dose vs. low-dose infections. In part, this increase is due to the local proliferation of pulmonary NK cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29717113/ccl4-enhances-preosteoclast-migration-and-its-receptor-ccr5-downregulation-by-rankl-promotes-osteoclastogenesis
#19
Dabin Lee, Kyung-Ju Shin, Dong Wook Kim, Kyung-Ae Yoon, Young-Jin Choi, Bom Nae Rin Lee, Je-Yoel Cho
Chemokine CCL4 (MIP-1β) is released from osteoblast cells to restore the homeostasis of hematopoietic stem cells during the activation of bone marrow. In this study, we investigated the function of CCL4 and its receptor CCR5 during osteoclastogenesis. CCL4 promoted the migration and viability of preosteoclast cells. However, CCL4 had no direct effect on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in mouse preosteoclast cells. In addition, CCR5 expression was rapidly reduced by RANKL treatment, which was recovered by IFN-γ during osteoclastogenesis...
May 2, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29708899/the-return-of-pro-140-a-ccr5-directed-mab
#20
Melanie A Thompson
PURPOSE OF REVIEW: Although antiretroviral therapy has become more potent and tolerable, adherence remains a barrier to continuous viral suppression and new approaches are needed. PRO 140 is a C-C chemokine receptor 5 (CCR5)-directed mAb with potential for weekly subcutaneous dosing. This review discusses data from the PRO 140 clinical development program including emerging data from ongoing efficacy studies. RECENT FINDINGS: Phase II development of PRO 140 began over a decade ago, and recently initiated phase IIb and III trials are ongoing in study participants with virologic failure and as monotherapy maintenance in virologically suppressed study participants...
April 27, 2018: Current Opinion in HIV and AIDS
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