title: Simian immunodeficiency virus dramatically alters expression of homeostatic chemokines and dendritic cell markers during infection in vivo.
abstract: Dendritic cells (DCs) are potent antigen-presenting cells that likely play multiple roles in human immunodeficiency virus type 1 (HIV-1) pathogenesis. We used the simian immunodeficiency virus (SIV)/macaque model to study the effects of infection on homeostatic chemokine expression and DC localization directly in secondary lymphoid tissues. SIV infection altered the expression of chemokines (CCL19/MIP-3beta, CCL21/ 6Ckine, and CCL20/MIP-3alpha) and of chemokine receptors (CCR7 and CCR6) that drive DC trafficking. CCL19/MIP-3beta, CCL20/MIP-3alpha, CCR6, and CCR7 expression increased in lymph nodes during the early systemic burst of viral replication (acute infection), whereas CCL21/6Ckine expression progressively decreased throughout disease to AIDS. Parallel with the SIV-induced perturbations in chemokine expression were changes in the expression of the DC-associated markers, DC-SIGN, DC-LAMP, and DECTIN-1. During AIDS, DC-LAMP mRNA expression levels were significantly reduced in lymph nodes and spleen, and DC-SIGN levels were significantly reduced in spleen. These findings suggest that the disruption of homeostatic chemokine expression is responsible, in part, for alterations in the networks of antigen-presenting cells in lymphoid tissues, ultimately contributing to systemic immunodeficiency.
authors.affiliation: Department of Infectious Diseases and Microbiology and the Department of Molecular Genetics and Biochemistry, University of Pittsburgh, PA.
authors.forename: Yang Kyu
authors.initials: YK
authors.lastname: Choi
authors.forename: Beth A
authors.initials: BA
authors.lastname: Fallert
authors.forename: Michael A
authors.initials: MA
authors.lastname: Murphey-Corb
authors.forename: Todd A
authors.initials: TA
authors.lastname: Reinhart
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054421:Chemokine CCL21; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D019742:Chemokines, CC / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D015967:Gene Expression Regulation, Viral; D006706:Homeostasis; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D051907:Lysosomal Membrane Proteins; D008253:Macaca mulatta; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D014779:Virus Replication; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000099181:Dectin-1
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D054421:Chemokine CCL21; D018925:Chemokines; D019742:Chemokines, CC; D037181:Lectins, C-Type; D051907:Lysosomal Membrane Proteins; D019402:Macrophage Inflammatory Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000099181:Dectin-1; C515460:CCL19 protein, human; C108355:CCL20 protein, human; C515478:CCL21 protein, human; C106311:CCR6 protein, human; C515370:CCR7 protein, human