title: A novel role for Slit2/Robo1 axis in modulating HIV-1 replication in T cells.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Pathology, Ohio State University Medical Center, Columbus, 43210, USA.
authors.forename: Appakkudal R
authors.initials: AR
authors.lastname: Anand
authors.lastname: Tirumuru Nagaraja
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ganju
mesh_terms: D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000821:virology; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation; D014779:Virus Replication / Q000276:immunology; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein