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https://www.readbyqxmd.com/read/28542587/seminal-plasma-induces-inflammation-and-enhances-hiv-1-replication-in-human-cervical-tissue-explants
#1
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/28542329/novel-agoshrna-molecules-for-silencing-of-the-ccr5-co-receptor-for-hiv-1-infection
#2
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/28539614/the-ccr5-antagonist-maraviroc-reverses-hiv-1-latency-in-vitro-alone-or-in-combination-with-the-pkc-agonist-bryostatin-1
#3
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/28534889/hiv-1-infection-in-persons-homozygous-for-ccr5-%C3%AE-32-allele-the-next-case-and-the-review
#4
Joanna Smoleń-Dzirba, Magdalena Rosińska, Janusz Janiec, Marek Beniowski, Mariusz Cycoń, Jolanta Bratosiewicz-Wąsik, Tomasz J Wąsik
CC-chemokine receptor 5 serves as the coreceptor for the HIV-1 R5 strains, which are responsible for the majority of HIV transmissions. A deletion of 32 nucleotides in the gene encoding this receptor (termed CCR5-Δ32) leads to the suppression of CC-chemokine receptor 5 presentation at the cell surface, thus impeding process of HIV entry into the cell. Individuals homozygous for the CCR5-Δ32 allele are resistant to infection with HIV-1 R5 strains, and are extremely rare among HIV-1-infected individuals. We have described a case of person homozygous for CCR5-Δ32, who was infected with subtype B HIV-1...
May 23, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28527722/crispr-cas9-mediated-ccr5-ablation-in-human-hematopoietic-stem-progenitor-cells-confers-hiv-1-resistance-in%C3%A2-vivo
#5
Lei Xu, Huan Yang, Yang Gao, Zeyu Chen, Liangfu Xie, Yulin Liu, Ying Liu, Xiaobao Wang, Hanwei Li, Weifeng Lai, Yuan He, Anzhi Yao, Liying Ma, Yiming Shao, Bin Zhang, Chengyan Wang, Hu Chen, Hongkui Deng
Transplantation of hematopoietic stem cells (HSCs) with a naturally occurring CCR5 mutation confers a loss of detectable HIV-1 in the patient, making ablation of the CCR5 gene in HSCs an ideal therapy for an HIV-1 cure. Although CCR5 disruption has been attempted in CD4(+) T cells and hematopoietic stem/progenitor cells (HSPCs), efficient gene editing with high specificity and long-term therapeutic potential remains a major challenge for clinical translation. Here, we established a CRISPR/Cas9 gene editing system in human CD34(+) HSPCs and achieved efficient CCR5 ablation evaluated in long-term reconstituted NOD/Prkdc(scid)/IL-2Rγ(null) mice...
May 17, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28527291/haplotypes-in-ccr5-ccr2-ccl3-and-ccl5-are-associated-with-natural-resistance-to-hiv-1-infection-in-a-colombian-cohort
#6
Jorge A Vega, Simón Villegas-Ospina, Wbeimar Aguilar-Jiménez, María T Rugeles, Gabriel Bedoya, Wildeman Zapata
INTRODUCTION: Variants in genes encoding for HIV-1 co-receptors and their natural ligands have been individually associated to natural resistance to HIV-1 infection. However, the simultaneous presence of these variants has been poorly studied. OBJECTIVE: To evaluate the association of single and multilocus haplotypes in genes coding for the viral co-receptors CCR5 and CCR2, and their ligands CCL3 and CCL5, with resistance or susceptibility to HIV-1 infection. MATERIALS AND METHODS: Nine variants in CCR5-CCR2, two SNPs in CCL3 and two in CCL5 were genotyped by PCR-RFLP in 35 seropositive (cases) and 49 HIV-1-exposed seronegative Colombian individuals (controls)...
June 1, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28526681/adoptive-transfer-of-phosphoantigen-specific-%C3%AE-%C3%AE-t-cell-subset-attenuates-mycobacterium-tuberculosis-infection-in-nonhuman-primates
#7
Arwa Qaqish, Dan Huang, Crystal Y Chen, Zhuoran Zhang, Richard Wang, Shengpu Li, Enzhuoa Yang, Yang Lu, Michelle H Larsen, William R Jacobs, Lixia Qian, James Frencher, Ling Shen, Zheng W Chen
The dominant Vγ2Vδ2 T cell subset recognizes phosphoantigen and exists only in humans and nonhuman primates. Despite the discovery of γδ T cells >30 y ago, a proof-of-concept study has not been done to prove the principle that the Vγ2Vδ2 T cell subset is protective against Mycobacterium tuberculosis and other infections. In this study, we used an adoptive cell-transfer strategy to define the protective role of Vγ2Vδ2 T cells in a primate tuberculosis (TB) model. Vγ2Vδ2 T cells for adoptive transfer displayed central/effector memory and mounted effector functions, including the production of anti-M...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28524801/association-of-ugt2b7-ugt1a9-abcg2-and-il23r-polymorphisms-with-rejection-risk-in-kidney-transplant-patients
#8
Heloísa Lizotti Cilião, Rossana Batista Oliveira Camargo-Godoy, Marilesia Ferreira de Souza, Mariana Bisarro Dos Reis, Lorena Iastrenski, Vinicius Daher Alvares Delfino, Silvia Regina Rogatto, Ilce Mara de Syllos Cólus
Despite advances in testing compatibility between donor and recipient, graft rejection remains a current concern. Single-nucleotide polymorphisms (SNPs) that codify altered enzymes of metabolism, drug transport, and the immune system may contribute to graft rejection in transplant patients. This study examined the association between SNPs present in genes of these processes and occurrence of graft rejection episodes in 246 kidney transplant patients, 35% of which were diagnosed with rejection. Genotype-gene expression associations were also assessed...
May 19, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28521443/loss-of-fas-expression-and-high-expression-of-hla-e-promoting-the-immune-escape-of-early-colorectal-cancer-cells
#9
Renxiang Huang, Dongyang Zhang, Feng Li, Zili Xiao, Meiling Wu, Dongyun Shi, Ping Xiang, Zhijun Bao
Previous studies have investigated the mechanisms of immune evasion of tumor cells in numerous types of advanced solid malignant tumor, and several types of immune preparations have been administered as antitumor adjuvant therapies. However, in the majority of studies, the efficacy of therapies has been revealed to be limited. The present study aimed to investigate the immune evasion mechanisms employed by early colorectal cancer cells and the expression of the molecules associated with immune evasion during the malignant transformation process of normal colorectal epithelial cells to measure the effects of immune intervention for early colorectal cancer, and to improve the efficacy of immunotherapy...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521215/adaptation-of-hiv-1-to-cells-with-low-expression-of-the-ccr5-coreceptor
#10
Nicole Espy, Beatriz Pacheco, Joseph Sodroski
The binding of the human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer ((gp120/gp41)3) to the receptors CD4 and CCR5 triggers virus entry into host cells. To identify Env regions that respond to CCR5 binding, HIV-1 was serially passaged on a CD4-positive canine cell line expressing progressively lower levels of CCR5. HIV-1 replication was observed in cells expressing ~1300 CCR5 molecules/cell. Env changes that conferred this low-CCR5 replication phenotype were located outside of the known CCR5-binding region of the gp120 Env subunit and did not apparently increase CCR5 binding affinity...
May 15, 2017: Virology
https://www.readbyqxmd.com/read/28518224/t-helper-1-related-molecules-as-well-as-il-15-are-hyperexpressed-in-the-skin-lesions-of-patients-with-pyoderma-gangrenosum
#11
Emiliano Antiga, Roberto Maglie, Walter Volpi, Beatrice Bianchi, Emilio Berti, Angelo Valerio Marzano, Marzia Caproni
Pyoderma gangrenosum (PG) is a rare, immune-mediated skin disease classified into the group of neutrophilic dermatoses. Whether a number of studies confirmed the central role of innate immunity, only few studies investigated the possible contributing role of acquired immunity. In particular, no reports about Th1 and Th2 cells are available yet. Therefore, 15 patients with PG, 5 with Sweet's syndrome (SS) and 9 skin specimens from healthy controls (HC) were investigated, evaluating the expression of Th1-related markers IL-12, IFN-γ, CXCR3, CCR5, of the Th2 related molecules IL-4, IL-5, IL-13 and CCR3, of the co-stimulatory axis CD40/CD40L, of IL-15 and the NK cell marker CD56 in skin lesions by immunohistochemistry...
May 18, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28515692/wu-tou-decoction-in-rheumatoid-arthritis-integrating-network-pharmacology-and-in-vivo-pharmacological-evaluation
#12
Qingqing Guo, Kang Zheng, Danping Fan, Yukun Zhao, Li Li, Yanqin Bian, Xuemei Qiu, Xue Liu, Ge Zhang, Chaoying Ma, Xiaojuan He, Aiping Lu
Purpose: This study aimed to explore underlying action mechanism of Wu-Tou decoction (WTD) in rheumatoid arthritis (RA) through network pharmacology prediction and experimental verification. Methods: Chemical compounds and human target proteins of WTD as well as RA-related human genes were obtained from TCM Database @ Taiwan, PubChem and GenBank, respectively. Subsequently, molecular networks and canonical pathways presumably involved in the treatment of WTD on RA were generated by ingenuity pathway analysis (IPA) software...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28509877/human-beta-defensin-2-selectively-inhibits-hiv-1-in-highly-permissive-ccr6%C3%A2-%C2%BAcd4%C3%A2-%C2%BA-t-cells
#13
Mark K Lafferty, Lingling Sun, Aaron Christensen-Quick, Wuyuan Lu, Alfredo Garzino-Demo
Chemokine receptor type 6 (CCR6)⁺CD4⁺ T cells are preferentially infected and depleted during HIV disease progression, but are preserved in non-progressors. CCR6 is expressed on a heterogeneous population of memory CD4⁺ T cells that are critical to mucosal immunity. Preferential infection of these cells is associated, in part, with high surface expression of CCR5, CXCR4, and α4β7. In addition, CCR6⁺CD4⁺ T cells harbor elevated levels of integrated viral DNA and high levels of proliferation markers...
May 16, 2017: Viruses
https://www.readbyqxmd.com/read/28501927/cytokine-gene-polymorphism-associations-with-congenital-cytomegalovirus-infection-and-sensorineural-hearing-loss
#14
B Kasztelewicz, J Czech-Kowalska, B Lipka, B Milewska-Bobula, M K Borszewska-Kornacka, J Romańska, K Dzierżanowska-Fangrat
Cytomegalovirus (CMV) is the most common viral agent of congenital infections and a leading nongenetic cause of sensorineural hearing loss (SNHL). The host immunologic factors that render a developing foetus prone to intrauterine CMV infection and development of hearing loss are unknown. The aim of this study was to assess the potential associations between the polymorphisms within cytokine and cytokine receptors genes, and the risk of congenital CMV infection, and the hearing outcome. A panel of 11 candidate single nucleotide polymorphisms (SNPs): TNF rs1799964, TNF rs1800629, TNFRSF1A rs4149570, IL1B rs16944, IL1B rs1143634, IL10 rs1800896, IL10RA rs4252279, IL12B rs3212227, CCL2 rs1024611, CCL2 rs13900, CCR5 rs333 was genotyped in 470 infants (72 with confirmed intrauterine CMV infection and 398 uninfected controls), and related to congenital CMV infection, and the outcome...
May 13, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28497977/effect-of-amino-acid-substitutions-within-the-v3-region-of-hiv-1-crf01_ae-on-interaction-with-ccr5-coreceptor
#15
Sayamon Hongjaisee, Martine Braibant, Francis Barin, Nicole Ngo-Giang-Huong, Wasna Sirirungsi, Tanawan Samleerat
Specific amino acids within the V3 loop of HIV-1 CRF01_AE envelope glycoprotein that are involved in the interaction with CCR5/CXCR4 coreceptors, are not well characterized. We generated V3 mutants using PCR-based site-directed mutagenesis of HIV-1 CRF01_AE R5-env plasmids at specific positions. Mutant viruses were produced by env-pseudotyped virus assay, tested for coreceptor usage using U373.R5 and U373.X4 cells, and viral entry was assessed with luciferase activity measurement. All viruses, harboring either single or double mutations, used the CCR5 coreceptor...
May 12, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28494757/copd-monocytes-demonstrate-impaired-migratory-ability
#16
Arjun K Ravi, Jonathan Plumb, Rosemary Gaskell, Sarah Mason, Caroline S Broome, George Booth, Matthew Catley, Jørgen Vestbo, Dave Singh
BACKGROUND: Increased lung macrophage numbers in COPD may arise from upregulation of blood monocyte recruitment into the lungs. CCR5 is a monocyte chemokine receptor regulated by interleukin-6 (IL-6); the concentration of CCR5 ligands are known to be elevated in COPD lungs. The objective of this study was to investigate mechanisms of monocyte recruitment to the lung in COPD, including the role of CCR5 signalling. METHODS: Ninety one COPD patients, 29 smokers (S) and 37 non-smokers (NS) underwent sputum induction, plasma sampling (to measure IL-6 and soluble IL-6 receptor [sIL-6R] by immunoassay), monocyte characterization (by flow cytometry) and monocyte isolation for cell migration and quantitative polymerase chain reaction studies...
May 11, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28494720/hla-c-single-nucleotide-polymorphism-associated-with-increased-viral-load-level-in-hiv-1-infected-individuals-from-northeast-brazil
#17
Ronaldo Celerino da Silva, Ronald Rodrigues de Moura, Antonio Victor Campos Coelho, Luiz Cláudio Arraes, Lucas André Cavalcanti Brandão, Sergio Crovella, Rafael Lima Guimarães
In our study we analyzed genetic variations in Human leukocyte antigen C (HLA-C), Zinc ribbon domain containing 1 (ZNRD1) and its antisense RNA (ZNRD1-AS1) genes, known to influence the HIV-1 replication and disease progression. We evaluated the distribution of HLA-C (rs10484554, rs9264942) and ZNRD1 (rs8321) and ZNRD1-AS1 (rs3869068), single nucleotide polymorphisms (SNPs) in 266 HIV-1-infected and 223 unexposed-uninfected individuals from Northeast Brazil. HLA-C SNPs were in Linkage Disequilibrium (D'=0.84), constituting four possible haplotypes...
May 11, 2017: Current HIV Research
https://www.readbyqxmd.com/read/28494151/design-of-hiv-co-receptor-derived-peptides-that-inhibit-viral-entry-at-submicromolar-concentrations
#18
Kostyantyn D Bobyk, Sivakoteswara R Mandadapu, Katheryn Lohith, Christina Guzzo, Abhishek Bhargava, Paolo Lusso, Carole A Bewley
HIV/AIDS continues to pose an enormous burden on global health. Current HIV therapeutics include inhibitors that target the enzymes HIV protease, reverse transcriptase and integrase, along with viral entry inhibitors that block the initial steps of HIV infection by preventing membrane fusion or virus-coreceptor interactions. With regard to the latter, peptides derived from the HIV coreceptor CCR5 were previously shown to modestly inhibit entry of CCR5-tropic HIV strains, with a peptide containing residues 178-191 of the second extracellular loop (peptide 2C) showing the strongest inhibition...
May 11, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28487238/the-recipient-ccr5-variation-predicts-survival-outcomes-after-bone-marrow-transplantation
#19
Tomohiro Horio, Shohei Mizuno, Kaori Uchino, Motonori Mizutani, Ichiro Hanamura, J Luis Espinoza, Makoto Onizuka, Koichi Kashiwase, Yasuo Morishima, Takahiro Fukuda, Yoshihisa Kodera, Noriko Doki, Koichi Miyamura, Takehiko Mori, Akiyoshi Takami
The chemokine receptor CCR5 plays roles in the trafficking of effector cells towards the site of inflammation. We retrospectively examined the impact of the CCR5 variation (rs1800023, -2086A>G) on transplant outcomes in a cohort of 329 patients who underwent unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies through the Japan Marrow Donor Program. A multivariate analysis showed that the recipient CCR5 -2086A/A genotype was significantly associated with a lower relapse rate but not with the development of graft-versus-host disease (GVHD) or transplant-related mortality, thereby resulting in better disease-free and overall survival rates than other variations...
May 6, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28484468/the-membrane-proximal-region-of-c-c-chemokine-receptor-type-5-participates-in-the-infection-of-hiv-1
#20
Yue Tan, Pei Tong, Junyi Wang, Lei Zhao, Jing Li, Yang Yu, Ying-Hua Chen, Ji Wang
The initial infection and transmission of HIV-1 requires C-C chemokine receptor type 5 (CCR5). Here, we report that the membrane-proximal region (MPR, aa 22-38) of CCR5 participates in the infection of HIV-1. First, MPR-specific antibodies elicited in mice dose-dependently inhibited the infection of CCR5-tropic HIV-1. Second, substituting MPR with the same region from other co-receptors significantly impaired HIV-1 infection, while the key residues identified by alanine scanning mutagenesis formed an exposed leucine zipper-like structure...
2017: Frontiers in Immunology
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