A novel role for Slit2/Robo1 axis in modulating HIV-1 replication in T cells.
A novel role for Slit2/Robo1 axis in modulating HIV-1 replication in T cells.
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DOI：
10.1097/qad.0b013e32834bab86
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发表时间：
2011-11-13
期刊：
影响因子：
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通讯作者：
Ganju RK
中科院分区：
文献类型：
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作者：
Anand AR;Tirumuru Nagaraja;Ganju RK
Slit2 is a secreted glycoprotein that has been shown to possess anti-inflammatory properties. In addition, Slit2 has been shown to modulate CXCR4-mediated functional effects in T cells. However, its role in HIV-1 pathogenesis is not known. The objective of the current study is to analyze the role of Slit2 in modulating HIV-1 replication in T cells. The effect of endogenous Slit2 expression of HIV-1 replication in T cells was studied by transient overexpression or downregulation of Slit2. The role of exogenous Slit2 was studied by analyzing the effect of soluble Slit2 protein on HIV-1 replication in T-cell lines and peripheral blood mononuclear cells (PBMCs). Studies on T-cell lines revealed a higher expression of Slit2 in Jurkat T cells compared with MT4 cells. We observed that downregulation of Slit2 in Jurkat T cells using Slit2-specific small inhibitor RNA enhanced HIV-1 replication. However, overexpression of Slit2 in MT4 cells and PBMCs reduced HIV-1 replication. As Slit2 is a secretory protein, we further analyzed the role of soluble Slit2 on HIV-1 virus replication using various cell lines and PBMCs. Our data indicated that exogenous Slit2 inhibited replication of both X4-tropic and R5-tropic HIV-1 viruses. Further studies revealed that Slit2 mediated its functional effects by binding to Robo1 receptor. Taken together, our results describe Slit2/Robo1 axis as a novel modulator of HIV-1 replication in T cells. These studies may contribute to the understanding of the immunopathogenesis of HIV-1 infection.
