1.Study of the mutation of the CCR5 and SDF1 gene in the HIV-1 infected mothers and their children
Anh Thi Thu Phan ; Thuy Thanh Nguyen ; Lan Thi Phuong Nguyen
Journal of Medical Research 2007;47(2):16-22
Background: HIV (human immunodeficiency virus) is the virus that causes AIDS. This virus is passed from one person to another through blood-to-blood and sexual contact. In addition, infected pregnant women can pass HIV to their baby during pregnancy or delivery, as well as through breast-feeding. Objectives:To study the CCR5- 32 and SDF 1-3 A allelic frequence in the HIV -1 infected mothers and their children. Subjects and method: Amplificated on CCR5 and SDF1 gene by PCR and restriction of this fragment length polymorphisme (RLFP) assay for detection of the mutated gene by EcoR1 and Hpall. Results: No mutation of CCR5 was found but only mutation identified at the SDF1 gene. Mutation identified at the SDF1 gene of the mother was: homozygote 2.7% (accounted for 2/37 cases), heterozygote 40.54% (accounted for 15/37 cases) and at the children: homozygote 5.4% (accounted for 1/37 cases), heterozygote 45.95% (accounted for 17/37 cases). The CCR5 chemokin receptor is a co-receptor for M trofic HIV-1 strains, which predominate in the early stage of the HIV disease and SDF-1 natural ligand for the CXCR4 reception. The mutation of these genes protect from HIV-1 infection (slow progression).\r\n', u'Conclusion: It\u2019s necessary to find the mutation of CCR5 and CCR2b related the progression of HIV patients. \r\n', u'
HIV-1/ metabolism
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Receptors
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CCR5
2.Research progress on chemokine receptor 5-targeted therapy for HIV-1.
Yan-Jie WANG ; Jan-Qiong ZHANG
Chinese Journal of Virology 2014;30(1):79-83
Along with the spread of human immunodeficiency virus 1 (HIV-1) infection in the world and the emergence of drug-resistant viral strains, it is urgent to seek the novel potent therapies. Chemokine receptor 5 (CCR5) is one of the main coreceptors involved in the entry of HIV-1 into target cells. Nowadays, a number of CCR5 antagonists have been developed and some of them have progressed to clinical trials or been approved. Research progress has also been made in the CCR5-targeted gene therapy. This review summarizes the recent research progress on the CCR5-targeted drug and gene therapy.
CCR5 Receptor Antagonists
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HIV Infections
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drug therapy
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genetics
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metabolism
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pathology
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HIV-1
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drug effects
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Humans
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Molecular Targeted Therapy
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methods
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Receptors, CCR5
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deficiency
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genetics
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metabolism
3.CCR5, a new target of anti-HIV drugs.
Yan-xing HAN ; Jian-dong JIANG
Acta Academiae Medicinae Sinicae 2003;25(5):635-639
CCR5, a membrane protein on cell surface, is a member of the G protein-coupled receptor superfamily and one of the major co-receptors for HIV-1 infection. The roles of CCR5 in HIV-1 infection have been elucidated since 1996. Because of the biological nature of CCR5, it has became a molecular target for the novel drugs against HIV-1. Antagonists for CCR5 could be grouped as following, chemokine derivatives, small molecule non-peptide compounds, monoclonal antibodies and peptides. The latest progress in this field is reviewed in this article.
Anti-HIV Agents
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pharmacology
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Antibodies, Monoclonal
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CCR5 Receptor Antagonists
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Drug Design
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HIV Infections
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metabolism
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HIV-1
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drug effects
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Receptors, CCR5
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drug effects
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Receptors, Chemokine
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drug effects
4.Relationship between CCR5 gene polymorphism and condyloma acuminata.
Ya-Gang ZUO ; Bao-Xi WANG ; Xiu-Rong LIU ; Peng ZHAO ; Qian-Shu YAN
Acta Academiae Medicinae Sinicae 2008;30(1):95-97
OBJECTIVETo investigate the relationship between CCR5 delta32 gene polymorphism and condyloma acuminata.
METHODSWe used polymerase chain reaction to amplify the CCR5 gene fragments in 60 patients with condyloma acuminata and 50 age- and sampling date-matched controls, and compared the difference of genotypes between these two groups.
RESULTSNo genotype difference was found between these two groups.
CONCLUSIONCondyloma acuminata are not associated with genetic polymorphism of CCR5 delta32 gene.
Condylomata Acuminata ; genetics ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymorphism, Genetic ; Receptors, CCR5 ; genetics
5.Construction of recombinant vectors expressing antisense RNA to CCR5 and expression in eukaryotic cells.
Huichun XING ; Xiaoyuan XU ; Qinhuan WANG ; Min YU ; Weibo GONG ; Yiming SHAO
Chinese Journal of Experimental and Clinical Virology 2002;16(1):52-54
BACKGROUNDTo construct recombinant vector expressing antisense RNA to CCR5 in eukaryotic cells and obtain recombinant pseudovirus, which will be used to block HIV-1 infection.
METHODSThe DNA fragment targeted against the initional part of CCR 5 mRNA translation was amplified by using RT-PCR from peripheral blood mononuclear cells (PBMCs) and cloned into retroviral vector pLXSN, then transfected into packaging cell (PA317) with lipofectAMINE. After 2-3 weeks selecting with G418, the pseudovirion in the survival cell's supernatant was detected with RT-PCR (FQ),then was used to infect NIH/3T3 cell.
RESULTSThe psuedovirion packed from expression vector of sense/antisense RNA to CCR5 had infected NIH/3T3 cell successfully. The vector had incorporated into its genome and transcripted into RNA.
CONCLUSIONSThe gene fragment of antisense RNA to CCR5 could be obtained from PBMCs and transfected into eukaryotic cell with retroviral vector. The results made a great foundation for studying its inhibiting effect on HIV-1 infection.
3T3 Cells ; Animals ; Eukaryotic Cells ; metabolism ; Gene Expression ; Genetic Vectors ; Mice ; Plasmids ; genetics ; RNA, Antisense ; genetics ; Receptors, CCR5 ; genetics ; Transfection
6.Chemokine Receptor-5 and Graft-versus-Host Disease.
Jing YUAN ; Wei LIU ; Han-Yun REN
Journal of Experimental Hematology 2015;23(3):883-887
Chemokine receptor-5 (CCR5) belongs to a G-protein coupled receptors superfamily. It is mainly expressed on a wide variety of immune cells. CCR5 can bind with its specific ligands, which plays very important roles in inflammatory cell growth, differentiation, activation, adhesion and migration. CCR5 was identified as a co-receptor for human immunodeficiency virus type-1 (HIV-1) to infect CD4+ T cells. In addition, CCR5 not only participates in the pathogenic mechanisms of many inflammation disease such as AIDS, auto-immune disease, and atherosclerosis, but also plays important roles in the development of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Recent studies using murine models have demonstrated the critical role of CCR5 and its ligands which direct T-cell infiltration and recruitment into target tissues during acute GVHD. CCR5 has become the focus of intense interest and discussion, and this review will attempt to describe what is understood about the structure and function, internalization, signal transduction of CCR5, in order to investigate the relationship between CCR5 and acute GVHD.
CD4-Positive T-Lymphocytes
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Cell Proliferation
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Graft vs Host Disease
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Hematopoietic Stem Cell Transplantation
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Humans
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Receptors, CCR5
7.Detection and preliminary study of a family carrying a CCR5Δ32 deletional mutation.
Chi ZHOU ; Hao SUN ; Jia-xiang YIN ; Hong-ying ZHANG ; Ke-qin LIN ; Yu-fen TAO ; Zhao-qing YANG ; Jia-you CHU ; Xiao-qin HUANG
Chinese Journal of Medical Genetics 2012;29(4):485-489
OBJECTIVETo investigate the frequencies of chemokine (C-C motif) receptor 5 gene (CCR5)Δ32 deletional mutation of in Han and Dai populations from Yunnan province. Immortalized cell lines were derived from a family carrying the CCR5Δ32 mutation.
METHODSBlood samples of 346 Han and 355 Dai individuals were collected for genotyping. The coding regions of CCR5 gene were amplified with PCR followed by agarose gel electrophoresis. Suspected mutations were verified with DNA sequencing. Immortalized cell lines were constructed by using Epstain Barr virus and cyclosporine A. The difference between the cell lines and original blood samples was verified with PCR.
RESULTSOne ethnic Han individual was confirmed to be heterozygous for a deletional mutation by sequencing, which has led to discovery of a family with CCR5Δ32. Nine immortalized cell lines were established from this family, and no difference between the cell lines and original blood samples was detected by PCR.
CONCLUSIONTogether with previous reports, this study has indicated a significant difference in CCR5Δ32 among different ethnic groups in China. Established immortalized cell lines can also provide material for future research.
Base Sequence ; China ; Ethnic Groups ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Molecular Sequence Data ; Pedigree ; Receptors, CCR5 ; genetics ; Sequence Deletion
8.Expression of chemokine receptor--CXCR3 and CCR5 in liver tissues of patients with hepatitis B.
Chun-wen PU ; Chun-meng JIANG ; Shu-rong CONG ; Da-peng MA
Chinese Journal of Hepatology 2005;13(9):708-709
Adult
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Female
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Hepatitis B, Chronic
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metabolism
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Humans
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Liver
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metabolism
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Male
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Receptors, CCR5
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biosynthesis
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genetics
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Receptors, CXCR3
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Receptors, Chemokine
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biosynthesis
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genetics
9.Identification of HIV-1 specific T lymphocyte responses in highly exposed persistently seronegative Chinese.
Hong-wei LIU ; Kun-xue HONG ; Jun MA ; Lin YUAN ; Sha LIU ; Jian-ping CHEN ; Yuan-zhi ZHANG ; Yu-hua RUAN ; Jian-qing XU ; Yi-ming SHAO
Chinese Medical Journal 2006;119(19):1616-1621
BACKGROUNDStudies of highly exposed persistently seronegative (HEPS) individuals may provide valuable information on mechanisms of protection and on vaccine design. Cellular immune responses play a critical role in containing human immunodeficiency virus. However, the cellular immune responses in HEPS individuals have not been thoroughly assessed at the entire viral genome level.
METHODSTen HEPS Chinese with a history of frequent penetrative vaginal intercourse (mean frequency, at least once a week), with some unprotected sexual contact occurring in the weeks or days immediately before enrollment, 25 HIV-1 seropositive individuals, 10 HIV-1-seronegative healthy individuals with low-risk sexual behavior and no history suggestive of exposure to HIV-1 infection were enrolled. HIV-1-specific T cell responses were comprehensively analyzed by an interferon-gamma Elispot assay against 770 overlapping peptides spanning all HIV-1 proteins.
RESULTSHIV-1-specific T-cell responses of interferon-gamma secretion were identified in 3 (30%) out of 10 HEPS individuals; the specific cytotoxic T lymphocytes were targeted at Pol (2/10), Env (2/10), and Tat (1/10). HIV-1-specific T-cell responses of interferon-gamma secretion were identified in 20 (80%) out of 25 seropositive intravenous drug users (IDUs), revealing that all HIV-1 proteins and protein subunits could serve as targets for HIV-1-specific CD8(+) T cell responses with 85% recognizing Gag, 80% recognizing Nef, 75% recognizing Pol, 60% recognizing Env, 55% recognizing Vpu, 45% recognizing Vpr, 20% recognizing Vif, 20% recognizing Tat and 15% recognizing Rev in these seropositive individuals. None of the seronegative healthy individuals gave the positive T-cell responses.
CONCLUSIONSAbout 30% of HEPS Chinese mounted HIV-1 specific T cell immune responses. Cell-mediated immunity against HIV-1 may be developed through non-productive infections.
Adult ; Female ; HIV Seronegativity ; immunology ; HIV-1 ; immunology ; Humans ; Interferon-gamma ; biosynthesis ; Male ; Receptors, CCR5 ; genetics ; T-Lymphocytes, Cytotoxic ; immunology
10.Detection and its clinical value of CCR5 and CCR7 in dendritic cells from patients with active rheumatoid arthritis.
Journal of Southern Medical University 2010;30(9):2067-2069
OBJECTIVETo detect the expressions of CCR5 and CCR7 on dendritic cells (DCs) in patients with rheumatoid arthritis (RA) in different phases of disease activity, and explore the relationship between the disease activity and the expression of chemokine receptors.
METHODSTwenty-eight patients with low, moderate and high disease activity and 10 normal control subjects were enrolled in this study. Peripheral blood was obtained from the subjects and the DCs were isolated. The expression of CCR5 and CCR7 on DCs were detected by flow cytometry, and the serum levels of rheumatoid factor (RF), C-reactive protein (CRP) and anti-CCP antibody (ACPA) were assessed. The correlation of the expressions of CCR5 and CCR7 to serum RF, CRP, and ACPA levels of the RA patients were analyzed.
RESULTSCompared to the normal control group, RA patients showed enhanced expressions of CCR5 and CCR7 on the DCs. A linear correlation was noted between CCR5 and CCR7 expressions on the DCs and the serum levels of RF and CRP, but not ACPA, in the RA patients.
CONCLUSIONThe expressions of CCR5 and CCR7 on the DCs may correlate to the disease activity of RA, and may serve as valuable indices in monitoring the disease activity and the efficacy of the treatment.
Adult ; Arthritis, Rheumatoid ; blood ; immunology ; Dendritic Cells ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Receptors, CCR5 ; metabolism ; Receptors, CCR7 ; metabolism