Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemokine receptor CCR5 is essential for human immunodeficiency virus (HIV) entry into the sensitive cells. The CCR5 inactivation is believed to be one of the promising approaches in HIV therapy, including gene therapy. A powerful mechanism that enables to regulate gene expression is RNA interference which could be exploited to knockdown CCR5 gene. Here, three artificial microRNAs directed against the human CCR5 receptor gene were generated and their silencing activity in indicator cells developed on the basis of the HT1080 cell line was evaluated. Multiplexing of two or more artificial microRNAs in one transcript has been demonstrated to enhance the gene silencing. A 95% reduction of the CCR5 expression has been achieved using the most efficient microRNA combination.
 ...
PMID:[Downregulation of human CCR5 receptor gene expression using artificial microRNAs]. 2388 79

C-C chemokine receptor 5 (CCR5) plays an essential role in HIV pathogenesis as the major coreceptor on CD4+ T cells used by HIV, yet the function of CCR5 on CD8 T cells is not well understood. Furthermore, the immunologic effects of the CCR5 inhibitor maraviroc (MVC), despite approval for clinical use, have not yet been well evaluated for their potential effects on cytotoxic T-cell responses. In this study, we characterized the development and function of CCR5+CD8+ T cells in rhesus macaques with or without Simian immunodeficiency virus (SIV) infection. We also investigated the effects of the CCR5 antagonist MVC on functional CCR5+CD8+ T-cell responses in vitro. The data show that CCR5+CD8+ T cells have an effector memory phenotype and increase with age in systemic and mucosal lymphoid tissues as a heterogeneous population of polyfunctional CD8 T cells. In addition, CCR5 is highly expressed on SIV gag-specific (CM9+) CD8+ T cells in SIV-infected macaques, yet CCR5+CD8+ T cells are significantly reduced in mucosal lymphoid tissues with disease progression. Furthermore, in vitro MVC treatment reduced activation and cytokine secretion of CD8+ T cells via a CCR5-independent pathway. These findings suggest that surface CCR5 protein plays an important role in differentiation and activation of CD8+ T cells. Although MVC may be helpful in reducing chronic inflammation and activation, it may also inhibit virus-specific CD8+ T-cell responses. Thus optimal use of CCR5 antagonists either alone or in combination with other drugs should be defined by further investigation.-Wang, X., Russell-Lodrigue, K. E., Ratterree, M. S., Veazey, R. S., Xu, H. Chemokine receptor CCR5 correlates with functional CD8+ T cells in SIV-infected macaques and the potential effects of maraviroc on T-cell activation.
 ...
PMID:Chemokine receptor CCR5 correlates with functional CD8+ T cells in SIV-infected macaques and the potential effects of maraviroc on T-cell activation. 3103 75