C-C chemokine receptor type five (CCR5): An emerging target for the control of HIV infection

Barmania, Fatima; Pepper, Michael Sean

doi:10.1016/j.atg.2013.05.004

Cited by 102 publications

(91 citation statements)

References 182 publications

(236 reference statements)

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“…We focused on the potential expression of the following trafficking-related molecules: CXCR2 as homing for inflamed tissues(30), CXCR5, CCR7 and CD62L as tissue-homing (31–33), CXCR3 as trafficking/residence for Th1 cells (34), CCR5 as tissue-homing for CD4 + T cells(35), and LFA-1 as surrogate T cell-APC interaction in tissues (36, 37). In agreement with the TEM phenotype, almost all of these expanded Vγ2Vδ2 T cells exclusively expressed high levels of CXCR3, CCR5 and LFA-1, but not CXCR2, CXCR5, CCR7 or CD62L [Supplemental, Fig.S1.(C)].…”

Section: Resultsmentioning

confidence: 99%

Adoptive Transfer of Phosphoantigen-Specific γδ T Cell Subset AttenuatesMycobacterium tuberculosisInfection in Nonhuman Primates

Qaqish

Huang

Chen

et al. 2017

The Journal of Immunology

112

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Dominant Vγ2Vδ2 T-cell subset recognizes phosphoantigen, and exist only in humans and nonhuman primates. Despite the discovery of γδ T cells for >30 years, a proof-of-concept (POC) study has not been done to prove the principle that Vγ2Vδ2 T-cell subset is protective against M. tuberculosis (Mtb) and other infections. Here, we employed adoptive cell transfer strategy to define protective role for Vγ2Vδ2 T cells in primate TB model. Vγ2Vδ2 T cells for adoptive transfer displayed central/effector memory and mounted effector functions of producing anti-Mtb cytokines and inhibiting intracellular mycobacteria. They also expressed CXCR3/CCR5/LFA-1 trafficking/tissue-resident phenotypes and consistently trafficked to the airway and retained there detectable from 6 hours through 7 days after adoptive transfer. Interestingly, the test group of macaques receiving transfer of Vγ2Vδ2 T cells at weeks 1 and 3 after high-dose 500 CFU Mtb infection exhibited significantly lower levels of Mtb infection burdens in lung lobes and extra-pulmonary organs than the control groups receiving PBL or saline. Consistently, adoptive transfer of Vγ2Vδ2 T cells attenuated TB pathology and contained lesions mostly in the infection-site of right caudal lung lobe, with no or reduced TB dissemination to other lobes, spleens or livers/kidneys whereas the controls showed widespread TB dissemination. The POC finding supports the view that dominant Vγ2Vδ2 T-cell subset may be included for the rational design of TB vaccine or host-directed therapy.

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Section: Resultsmentioning

confidence: 99%

Adoptive Transfer of Phosphoantigen-Specific γδ T Cell Subset AttenuatesMycobacterium tuberculosisInfection in Nonhuman Primates

Qaqish

Huang

Chen

et al. 2017

The Journal of Immunology

112

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“…Reduced levels of CXCR4 mRNA transcripts were observed in cells infected with CD4-independent HIV-1 isolate [25]. Furthermore, the modulation of CCR5 expression by the HIV viruses is at the level of transcription [30]. Further experiments will be needed to determine the mechanisms of down-modulation of surface CXCR4 by HIV-1.…”

Section: Journal Of Hiv and Retro Virus Issn 2471-9676mentioning

confidence: 99%

Expression Analysis of Cell Surface Markers: Cluster of Differentiation 4, Chemokine Receptor 5 and C-X-C Chemokine Receptor Type 4 in Different Cell Lines after Infection with HIV

Balakrishna¹,

Gupta²,

Sridevi³

2018

J HIV Retrovirus

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The host cell infection by Human Immunodeficiency Virus (HIV) is initiated through the entry of the virus into the cell. The major target cells of HIV are cluster of differentiation 4 (CD4)+ T lymphocytes, which express co-receptors, chemokine receptor 5 (CCR5) or C-X-C chemokine receptor type 4 (CXCR4). HIV-1 envelope glycoprotein 120 (Gp120) binds to its primary receptor CD4, a member of the immunoglobulin superfamily enhances T-Cell Receptor (TCR)-mediated signaling, is absolutely required for the infection. Recent reports on cell surface marker expression levels by infecting CD4+ T cells with HIV-1 viruses gave an insight into host cell responses. In our study, we infected Jurkat, SupT1 cells and PBMCs with HIV-1 and analyzed the expression of cell surface markers gp120, CD4, CCR5 and CXCR4 levels by quantitative real time PCR (qRT-PCR) at different time intervals of post infection. Our study shows that there is ~ 5-fold increase in expression of gp120 1 h post infection and 1.5-fold increase in relative expression of CD4 and CCR5 at 2 h post infection, whereas CXCR4 showed differential up-regulation in different cell lines which needs further analysis.

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“…To date investigations have largely involved advancing therapeutic nucleic acids for management of hepatitis B virus (HBV) [5][6][7][8] and HIV-1 infections. 9,10 A particularly powerful feature of gene therapy is that design of candidate drugs is based on rational design that is essentially based on information about nucleic acid sequences. 2,3 Recent impressive progress of sequencing technology, coupled with advances in broader fields of molecular biology, virology, oncology and synthetic chemistry, amongst others, have provided valuable resources for advancing gene therapies.…”

Section: Introductionmentioning

confidence: 99%

The state of gene therapy research in Africa, its significance and implications for the future

et al. 2017

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Gene therapy has made impressive recent progress and has potential for treating a wide range of diseases, many of which are important to Africa. However, as a result of lack of direct public funding and skilled personnel, direct research on gene therapy in Africa is currently limited and resources to support the endeavor are modest. A strength of the technology is that it is based on principles of rational design, and the tools of gene therapy are now highly versatile. For example gene silencing and gene editing may be used to disable viral genes for therapeutic purposes. Gene therapy may thus lead to cure from infections with HIV-1, hepatitis B virus and Ebola virus, which are of significant public health importance in Africa. Although enthusiasm for gene therapy is justified, significant challenges to implementing the technology remain. These include ensuring efficient delivery of therapeutic nucleic acids to target cells, limiting unintended effects, cost and complexity of treatment regimens. In addition, implementation of effective legislation that will govern gene therapy research will be a challenge. Nevertheless, it is an exciting prospect that gene therapy should soon reach the mainstream of medical management. Participation of African researchers in the exciting developments is currently limited, but their involvement is important to address health problems, develop capacity and enhance economic progress of the continent.

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C-C chemokine receptor type five (CCR5): An emerging target for the control of HIV infection

Cited by 102 publications

References 182 publications

Adoptive Transfer of Phosphoantigen-Specific γδ T Cell Subset AttenuatesMycobacterium tuberculosisInfection in Nonhuman Primates

Adoptive Transfer of Phosphoantigen-Specific γδ T Cell Subset AttenuatesMycobacterium tuberculosisInfection in Nonhuman Primates

Expression Analysis of Cell Surface Markers: Cluster of Differentiation 4, Chemokine Receptor 5 and C-X-C Chemokine Receptor Type 4 in Different Cell Lines after Infection with HIV

The state of gene therapy research in Africa, its significance and implications for the future

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