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https://www.readbyqxmd.com/read/28087520/atheroprotective-vaccination-with-mhc-ii-restricted-apob-peptides-induces-peritoneal-il-10-producing-cd4-t-cells
#1
Takayuki Kimura, Kevin Tse, Sara McArdle, Teresa Gerhardt, Jacqueline Miller, Zbigniew Mikulski, John Sidney, Alessandro Sette, Dennis Wolf, Klaus Ley
Although immunization with MHC class II-restricted ApoB peptides has been shown to be atheroprotective, the mechanism is unclear. Here, we investigated CD4(+) T cell populations in immunized atherosclerotic mice. Peptides (16-mers) from mouse ApoB, the core protein of low-density lipoprotein (LDL), were screened for binding to I-A(b) by computer prediction and confirmed by radiolabeled peptide competition. Three new peptides, P101 (FGKQGFFPDSVNKALY, 5.5 nM IC50), P102 (TLYALSHAVNSYFDVD, 6.8 nM), and P103 (LYYKEDKTSLSASAAS, 95 nM) were tested in an atherosclerosis model (Apoe(-/-) mice on western diet)...
January 13, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28073289/generation-and-characterization-of-hiv-1-transmitted-and-founder-virus-consensus-sequence-from-intravenous-drug-users-in-xinjiang-china
#2
Fan Li, Liying Ma, Yi Feng, Jing Hu, Na Ni, Yuhua Ruan, Yiming Shao
HIV-1 transmission in intravenous drug users (IDUs) have been characterized by high genetic multiplicity, suggests a greater challenge for HIV-1 infection blocking. We investigated a total of 749 sequences of full length gp160 gene obtained by single genome sequencing(SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence(IDU.CON). All the T/F virus was classified as subtype CRF07_BC, and predicted to be CCR5-tropic virus...
January 10, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28072843/chemokine-ligand-5-ccl5-derived-from-endothelial-colony-forming-cells-ecfcs-mediates-recruitment-of-smooth-muscle-progenitor-cells-spcs-toward-critical-vascular-locations-in-moyamoya-disease
#3
Ji Hoon Phi, Naoko Suzuki, Youn Joo Moon, Ae Kyung Park, Kyu-Chang Wang, Ji Yeoun Lee, Seung-Ah Choi, Sangjoon Chong, Reizo Shirane, Seung-Ki Kim
The etiology and pathogenesis of moyamoya disease (MMD) are still obscure. Previous studies indicated that angiogenic chemokines may play an important role in the pathogenesis of the disease. Recently, it was discovered that peripheral blood-derived endothelial colony-forming cells (ECFCs) and smooth muscle progenitor cells (SPCs) have defective functions in MMD patients. Therefore, the interaction of ECFCs and SPCs, the precursors of two crucial cellular components of vascular walls, with some paracrine molecules is an intriguing subject...
2017: PloS One
https://www.readbyqxmd.com/read/28064231/effects-of-therapy-with-maraviroc-on-the-carotid-intima-media-thickness-in-hiv-1-hcv-co-infected-patients
#4
Paolo Maggi, Giuseppe Bruno, Francesco Perilli, Annalisa Saracino, Anna Volpe, Carmen Santoro, Nicoletta Ladisa, Gioacchino Angarano
AIM: To evaluate, in human immunodeficiency virus-hepatitis C virus co-infected patients, the impact of C-C chemokine receptor type 5 (CCR5) antagonist maraviroc-based antiretroviral therapy on the carotid intima media thickness and on atheromasic plaques. PATIENTS AND METHODS: In this pilot prospective study, 12 HIV-HCV co-infected patients underwent color-Doppler ultrasonography before and 48 weeks after switching to a dual therapy based on maraviroc plus protease inhibitors boosted with ritonavir...
January 2017: In Vivo
https://www.readbyqxmd.com/read/28061826/monophylogenetic-hiv-1c-epidemic-in-ethiopia-is-dominated-by-ccr5-tropic-viruses-an-analysis-of-a-prospective-country-wide-cohort
#5
Amare Worku Kalu, Nigus Fikrie Telele, Solomon Gebreselasie, Daniel Fekade, Samir Abdurahman, Gaetano Marrone, Anders Sönnerborg
BACKGROUND: CCR5 coreceptor using HIV-1 subtype C (HIV-1C) has been reported to dominate the Ethiopian epidemic. However, almost all data have been obtained from two large cities in the central and north-west regions and recent data is lacking. METHODS: Plasma were obtained from 420 treatment-naïve patients recruited 2009-2011 to a large country-wide Ethiopian cohort. The V3 region was sequenced and the co-receptor tropism was predicted by the clinical and clonal models of the geno2pheno tool at different false positive rates (fpr) and for subtype...
January 6, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28060951/hiv-infects-bronchial-epithelium-and-suppresses-components-of-the-mucociliary-clearance-apparatus
#6
S Chinnapaiyan, T Parira, R Dutta, M Agudelo, A Morris, M Nair, H J Unwalla
Recurrent lung infections and pneumonia are emerging as significant comorbidities in the HIV-infected population in the era of combination antiretroviral therapy (cART). HIV infection has been reported to suppress nasal mucociliary clearance (MCC). Since the primary components driving nasal MCC and bronchial MCC are identical, it is possible that bronchial MCC is affected as well. Effective MCC requires optimal ciliary beating which depends on the maintenance of the airway surface liquid (ASL), a function of cystic fibrosis transmembrane conductance regulator (CFTR) activity and the integrity of the signaling mechanism that regulates ciliary beating and fluid secretion...
2017: PloS One
https://www.readbyqxmd.com/read/28059045/computational-screening-of-ccr5-inhibitors-as-potential-entry-inhibitor-microbicides-using-3d-qsar-studies-docking-and-molecular-dynamics-simulation
#7
Radhika Ramachandran, Muthusankar Aathi, D Durairaj Ruban, Shanmughavel Piramanyagam
BACKGROUND: The chemokine receptor CCR5 acts as a co-receptor for HIV binding and it is considered as an important target by CCR5 antagonists. Entry inhibitor based microbicides gain much importance nowadays as these drugs act at an early stage of HIV lifecycle and thus hinder the viral replication process in humans. The present study intends to identify a CCR5 antagonist which could be developed as a microbicide using computational approaches. METHOD: The pharmacophore modeling and 3D QSAR studies was used to identify CCR5 antagonists with enhanced antagonist activity...
January 6, 2017: Current HIV Research
https://www.readbyqxmd.com/read/28057639/clinical-and-immunologic-impact-of-ccr5-blockade-in-graft-versus-host-disease-prophylaxis
#8
Ryan H Moy, Austin P Huffman, Lee P Richman, Lisa Crisalli, Ximi K Wang, James A Hoxie, Rosemarie Mick, Stephen G Emerson, Yi Zhang, Robert H Vonderheide, David L Porter, Ran Reshef
Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Lymphocyte trafficking via chemokine receptors such as CCR5 plays a critical role in alloreactive responses, and previous data suggest that CCR5 blockade with maraviroc results in a low incidence of visceral GVHD. However, the full scope of clinical and immunologic effects of CCR5 blockade in HSCT has not been described. We compared a cohort of patients enrolled on a trial of reduced-intensity allo-HSCT with standard GVHD prophylaxis plus maraviroc to a contemporary control cohort receiving standard GVHD prophylaxis alone...
January 5, 2017: Blood
https://www.readbyqxmd.com/read/28053515/gender-differences-in-the-t-cell-profiles-of-the-airways-in-copd-patients-associated-with-clinical-phenotypes
#9
Helena Forsslund, Mingxing Yang, Mikael Mikko, Reza Karimi, Sven Nyrén, Benita Engvall, Johan Grunewald, Heta Merikallio, Riitta Kaarteenaho, Jan Wahlström, Åsa M Wheelock, C Magnus Sköld
T lymphocytes are believed to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). How T cells are recruited to the lungs and contribute to the inflammatory process is largely unknown. COPD is a heterogeneous disease, and discriminating disease phenotypes based on distinct molecular and cellular pathways may provide new approaches for individualized diagnosis and therapies. Bronchoalveolar lavage (BAL) and blood samples were obtained from 40 never-smokers, 40 smokers with normal lung function, and 38 COPD patients...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28053103/cytokines-elevated-in-hiv-elite-controllers-reduce-hiv-replication-in-vitro-and-modulate-hiv-restriction-factor-expression
#10
Evan S Jacobs, Sheila M Keating, Mohamed Abdel-Mohsen, Stuart L Gibb, John W Heitman, Heather C Inglis, Jeffrey N Martin, Jinbing Zhang, Zhanna Kaidarova, Xutao Deng, Shiquan Wu, Kathryn Anastos, Howard Crystal, Maria C Villacres, Mary Young, Ruth M Greenblatt, Alan L Landay, Stephen J Gange, Steven G Deeks, Elizabeth T Golub, Satish K Pillai, Philip J Norris
: A subset of HIV infected individuals termed elite controllers (ECs) maintain CD4+ T cell counts and control viral replication in the absence of antiretroviral therapy (ART). Systemic cytokine responses may differentiate ECs from subjects with uncontrolled viral replication or those who require ART to suppress viral replication. We measured 87 cytokines in four groups of women: 73 EC, 42 with pharmacologically suppressed viremia (ART), 42 with uncontrolled viral replication (noncontrollers, NC), and 48 HIV uninfected (NEG) subjects...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28052516/detection-of-intermolecular-transferred-noe-interactions-in-small-and-medium-size-protein-complexes-rantes-complexed-with-a-ccr5-n-terminal-peptide
#11
Meital Abayev, Gautam Srivastava, Boris Arshava, Fred Naider, Jacob Anglister
NMR is a powerful tool to study structural details of protein/peptide complexes exhibiting weak to medium binding (KD >10 µM). However, it has been assumed that intermolecular nuclear Overhauser effect (NOE) interactions are difficult to observe in such complexes. We demonstrate that intermolecular NOEs can be revealed by combining the (13) C-edited/(13) C-filtered experiment with the transferred-NOE effect (TRNOE). Due to the TRNOE phenomenon intermolecular NOE cross peaks are characterized by both the chemical shifts of the protein protons and the average chemical shifts of the peptide protons, which are dominated by the chemical shifts of the protons of the free peptide...
January 4, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28051087/effects-of-depot-medroxyprogesterone-acetate-on-the-immune-microenvironment-of-the-human-cervix-and-endometrium-implications-for-hiv-susceptibility
#12
K K Smith-McCune, J F Hilton, U Shanmugasundaram, J W Critchfield, R M Greenblatt, D Seidman, S Averbach, L C Giudice, B L Shacklett
Depot-medroxyprogesterone acetate is a commonly used injectable contraceptive that has been associated with an increased risk of HIV acquisition. This study compares effects of depot-medroxyprogesterone acetate on immune parameters from several upper reproductive tract compartments relevant to HIV-1 susceptibility in repetitive samples from 15 depot-medroxyprogesterone acetate users and 27 women not on hormonal contraceptives. Compared with samples from unexposed women in the mid-luteal phase, depot-medroxyprogesterone acetate use was associated with: increased endocervical concentrations of MCP1 and IFNalpha2; decreased endocervical concentrations of IL1beta and IL6; increased proportions of endometrial CD4+ and CD8+ cells expressing the activation marker HLADR; increased density of endometrial macrophages; and decreased density of endometrial regulatory T cells...
January 4, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28042947/efficient-transduction-of-human-and-rhesus-macaque-primary-t-cells-by-a-modified-human-immunodeficiency-virus-type-1-hiv-1-based-lentiviral-vector
#13
Huan He, Jing Xue, Weiming Wang, Lihong Liu, Chaobaihui Ye, Zhe Cong, Jason Kimata, Chuan Qin, Paul Zhou
HIV-1-based lentiviral vectors efficiently transduce genes to human, but not rhesus, primary T cells and hematopoietic stem cells (HSCs). The poor transduction of HIV-1 vectors to rhesus cells is mainly due to species-specific restriction factors such as rhesus TRIM5α. Previously, several strategies to modify HIV-1 vectors were developed to overcome rhesus TRIM5α restriction. While the modified HIV-1 vectors efficiently transduce rhesus HSCs, they remain suboptimal for rhesus primary T cells. Recently, HIV-1 variants that encode combinations of LNEIE mutations in capsid (CA) protein and SIVmac239 Vif were found to replicate efficiently in rhesus primary T cells...
January 2, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28042001/relationship-between-ccr5-wt-%C3%AE-32-heterozygosity-and-hiv-1-reservoir-size-in-adolescents-and-young-adults-with-perinatally-acquired-hiv-1-infection
#14
Marta Martínez-Bonet, A González-Serna, Maria Isabel Clemente, Sara Morón-López, Laura Díaz, Marisa Navarro, Maria C Puertas, Manuel Leal, Ezequiel Ruiz-Mateos, Javier Martinez-Picado, Maria Angeles Muñoz Fernández
BACKGROUND: Several host factors contribute to HIV disease progression in the absence of combination antiretroviral therapy (cART). Among them, the CC-chemokine receptor 5 (CCR5) is known to be the main coreceptor used by HIV-1 to enter target cells during the early stages of an HIV-1 infection. OBJECTIVE: We evaluated the association of CCR5((WT/Δ32)) heterozygosity with HIV-1 reservoir size, lymphocyte differentiation, activation and immunosenescence in adolescents and young adults with perinatally acquired HIV-infection receiving cART...
December 29, 2016: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28028680/establishment-of-mouse-leukemia-cell-lines-expressing-human-cd4-ccr5-using-lentiviral-vectors
#15
Ya-Jing Li, Fu-Yan ZhuGe, Chang-Chun Zeng, Jin-Yang He, Ning Tan, Juan Liang
A low-cost rodent model of HIV infection and which presents high application value is an effective tool to investigate HIV infection and pathogenesis. However, development of such a small animal model has been hampered by the unsuitability of rodent cells for HIV-1 replication given that the retrovirus HIV-1 has high selectivity to its host cell. Our study used the mouse leukemia cell lines L615 and L1210 that were induced by murine leukemia virus and transfected with hCD4/CCR5 loaded-lentiviral vector. Lentiviral vectors containing the genes hCD4/CCR5 under the transcriptional control of cytomegalovirus promoter were designed...
December 28, 2016: Virus Genes
https://www.readbyqxmd.com/read/28025070/a-recombinant-vesicular-stomatitis-virus-encoding-ccr5-tropic-hiv-1-receptors-targets-hiv-1-infected-cells-and-controls-hiv-1-infection
#16
Kazu Okuma, Koji Fukagawa, Takuya Kohma, Youichi Takahama, Yukio Hamaguchi, Mamoru Ito, Yuetsu Tanaka, Linda Buonocore, John K Rose, Isao Hamaguchi
Anti-retroviral therapy is useful to treat human immunodeficiency virus type 1 (HIV-1)-infected individuals, but has some major problems, such as the generation of multidrug-resistant viruses. To develop a novel supplemental or alternative therapeutic for CCR5-tropic (R5) HIV-1 infection, we generated a recombinant vesicular stomatitis virus (rVSV) in which the gene encoding its envelope glycoprotein (G) was replaced with the genes encoding R5 HIV-1 receptors (human CD4 and CCR5), designated VSVΔG-CC5. Our present data demonstrate that this rVSV specifically infects cells that are transiently expressing R5 HIV-1 envelope glycoproteins, but does not infect those expressing CXCR4-tropic HIV-1 envelope glycoproteins...
December 24, 2016: Microbes and Infection
https://www.readbyqxmd.com/read/28011329/functional-role-of-ccl5-rantes-for-hcc-progression-during-chronic-liver-disease
#17
Antje Mohs, Nadine Kuttkat, Johanna Reißing, Henning Wolfgang Zimmermann, Roland Sonntag, Amanda Proudfoot, Sameh A Youssef, Alain de Bruin, Francisco Javier Cubero, Christian Trautwein
BACKGROUND & AIMS: During liver inflammation, triggering fibrogenesis and carcinogenesis immune cells play a pivotal role. In the present study we investigated the role of CCL5 in human and in murine models of chronic liver inflammation leading to HCC development. METHODS: CCL5 expression and its receptors were studied in well-defined patients with chronic liver disease (CLD) and in two murine inflammation based HCC models. The role of CCL5 in inflammation, fibrosis, tumor initiation and progression was analyzed in different cell populations of NEMO(Δhepa)/CCL5(-/-) animals and after bone marrow transplantation (BMT)...
December 20, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/28009639/increased-expression-of-the-type-i-interferon-receptor-on-cd4-t-lymphocytes-in-hiv-1-infected-individuals
#18
M Scott Killian, Sue H Fujimura, Ramu G Sudhagoni
BACKGROUND: Type I interferons (IFN1; e.g. IFN-α and IFN-β) are potent cytokines that inhibit the replication of human immunodeficiency virus-1 (HIV-1) and other viruses. The antiviral and immunoregulatory activities of IFN1 are mediated through ligand/receptor interactions with the IFN1 receptor complex (IFNAR). Variation in the cell surface density of IFNAR could play a role in HIV-1 pathogenesis. METHODS: In this cross-sectional study of fresh whole blood, we used flow cytometry to evaluate the expression of IFNAR2 on lymphocyte subsets from HIV-1-infected (n=33) and -uninfected (n=22) individuals...
December 22, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28008933/class-b-%C3%AE-arrestin2-dependent-ccr5-signalosome-retention-with-natural-antibodies-to-ccr5
#19
Assunta Venuti, Claudia Pastori, Rosamaria Pennisi, Agostino Riva, Maria Teresa Sciortino, Lucia Lopalco
CCR5 stimulation with natural ligands, such as RANTES, classically induces short-term internalization with transient activation of β-arrestins and rapidly recycling on the cell surface. Here we discovered that, in T cells, natural CCR5 antibodies induce a CCR5-negative phenotype with the involvement of β-arrestin2, which leads to the formation of a stable CCR5 signalosome with both β-arrestin2 and ERK1. The activation of β-arrestin2 is necessary to CCR5 signaling for the signalosome formation and stabilization...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28007920/role-of-il-32-in-hiv-reactivation-and-its-link-to-hiv-hsv-coinfection
#20
Pedro M M Mesquita, Paula Preston-Hurlburt, Marla J Keller, Nalini Vudattu, Lilia Espinoza, Michelle Altrich, Kathryn Anastos, Kevan C Herold, Betsy C Herold
BACKGROUND: HSV-2 exacerbates HIV by unclear mechanisms. These studies tested the impact of HSV-2 on systemic T cell populations and HIV reservoirs. METHODS: Peripheral blood mononuclear cells from HIV-infected women on antiretroviral therapy who were HSV-2 seropositive or seronegative (HIV(+)/HSV-2(+) or HIV(+)/HSV-2(-)) and HIV-uninfected controls were analyzed by flow cytometry. HIV cell-associated (CA)-DNA and RNA were quantified in the absence or presence of activating stimuli, recombinant IL-32γ, and a RUNX1 inhibitor...
December 22, 2016: Journal of Infectious Diseases
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