OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.
OBJECTIVE: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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.
Authors: Bo Chen; Donald G Blair; Sergei Plisov; Gennady Vasiliev; Alan O Perantoni; Qian Chen; Meropi Athanasiou; Jane Y Wu; Joost J Oppenheim; De Yang Journal: J Immunol Date: 2004-11-15 Impact factor: 5.422
Authors: Ya-Lin Chiu; Vanessa B Soros; Jason F Kreisberg; Kim Stopak; Wes Yonemoto; Warner C Greene Journal: Nature Date: 2005-04-13 Impact factor: 49.962