title: Galectin-9 binding to Tim-3 renders activated human CD4+ T cells less susceptible to HIV-1 infection.
abstract: Galectin-9 (Gal-9) is a tandem repeat-type member of the galectin family and is a ligand for T-cell immunoglobulin mucin domain 3 (Tim-3), a type-I glycoprotein that is persistently expressed on dysfunctional T cells during chronic infection. Studies in autoimmune diseases and chronic viral infections show that Tim-3 is a regulatory molecule that inhibits Th1 type immune responses. Here we show that soluble Gal-9 interacts with Tim-3 expressed on the surface of activated CD4(+) T cells and renders them less susceptible to HIV-1 infection and replication. The Gal-9/Tim-3 interaction on activated CD4(+) T cells, leads to down-regulation of HIV-1 coreceptors and up-regulation of the cyclin-dependent kinase inhibitor p21 (also known as cip-1 and waf-1). We suggest that higher expression of Tim-3 during chronic infection has evolved to limit persistent immune activation and associated tissue damage. These data demonstrate a novel mechanism for Gal-9/Tim-3 interactions to induce resistance of activated CD4(+) T cells to HIV-1 infection and suggest that Gal-9 may play a role in HIV-1 pathogenesis and could be used as a novel microbicide to prevent HIV-1 infection.
authors.affiliation: Viral Vaccine Program, Seattle Biomedical Research Institute (Seattle Biomed), 307 Westlake Ave N, Seattle, WA 98109, USA.
authors.forename: Shokrollah
authors.initials: S
authors.lastname: Elahi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
authors.forename: Mitsuomi
authors.initials: M
authors.lastname: Hirashima
authors.forename: Helen
authors.initials: H
authors.lastname: Horton
mesh_terms: D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D002478:Cells, Cultured / Q000821:virology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D037161:Galectins / Q000378:metabolism*; D005786:Gene Expression Regulation; D016158:Genes, p53; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D034741:RNA, Small Interfering / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics; D054380:Receptors, CXCR5 / Q000096:biosynthesis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D019562:Viral Load; D014766:Viremia / Q000276:immunology*; D053585:Virus Attachment; D014779:Virus Replication
chemical_list: C493956:CDKN1A protein, human; C527276:CXCR4 protein, human; C095085:CXCR5 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D016023:Integrins; C105032:LGALS9 protein, human; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; D054380:Receptors, CXCR5; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C071777:integrin alpha4beta7