Báo cáo y học: "WFDC1 expression identifies memory CD4 Tlymphocytes rendered vulnerable to cell-cell HIV-1 transfer by promoting intercellular adhesive junctions"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: WFDC1 expression identifies memory CD4 Tlymphocytes rendered vulnerable to cell-cell HIV-1 transfer by promoting intercellular adhesive junctions. | Alvarez et al. Retrovirology 2011 8 29 http content 8 1 29 RETR0VIR0L0GY RESEARCH Open Access WFDC1 expression identifies memory CD4 T-lymphocytes rendered vulnerable to cell-cell HIV-1 transfer by promoting intercellular adhesive junctions Raymond A Alvarez Georgina Thorborn James L Reading Shalini Kamu Reddy and Annapurna Vyakarnam Abstract Background Elucidating mechanisms that promote HIV-1 transfer between CD4 T-lymphocytes and their subsequent loss is of importance to HIV-1 pathogenesis. We recently reported that whey acidic protein ps20 promotes cell-free HIV-1 spread through ICAM-1 modulation. Since ICAM-1 is pivotal in cell conjugation and intercellular HIV-1 transfer this study examines ps20 effects on HIV-1 spread between T lymphocytes. Results We demonstrate intrinsic ps20 variability in primary CD4 T-lymphocyte clonal populations and a significant positive correlation between endogenous ps20 levels and virus transfer involving fusion resulting in a spreading infection that could be reversed by the addition of reverse transcriptase inhibitors. Blocking anti-ps20 antibody or siRNA mediated ps20 knockdown significantly reduced virus transfer. Conversely virus transfer was promoted by ectopic ps20 expression or by exogenous addition of recombinant ps20. A higher frequency of virological synapse formation was evident in cocultures of HIV-1 infected donor T-cells with ps20high v ps20low intermediate targets. Blocking ps20 inhibited T-lymphocyte conjugate formation and ICAM-1 expression and was as potent as ICAM-1 in inhibiting HIV-1 transfer. Conclusions Therefore ps20 is a novel marker of CD4 T-cells rendered vulnerable to HIV-1 infection by regulating the fundamental biologic process of intercellular conjugate formation and consequently of potential importance in HIV-1 pathogenesis. Background Understanding the mechanisms by which retroviruses spread from one cell to another is of central importance to disease pathogenesis as this .

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