title: Measles virus modulates human T-cell somatostatin receptors and their coupling to adenylyl cyclase.
abstract: The possible role of immunomodulatory peptide somatostatin (SRIF) in measles virus (MV)-induced immunopathology was addressed by analysis of SRIF receptors and their coupling to adenylyl cyclase in mitogen-stimulated Jurkat T cells and human peripheral blood mononuclear cells (PBMC). SRIF-specific receptors were assayed in semipurified membrane preparations by using SRIF14 containing iodinated tyrosine at the first position in the amino acid chain ([125I]Tyr1) as a radioligand. A determination of receptor number by saturation of radioligand binding at equilibrium showed that in Jurkat cells, MV infection led to a dramatic decrease in the total receptor number. The virus-associated disappearance of one (Ki2 = 12 +/- 4 nM [mean +/- standard error of the mean [SEM]]; n = 4) of two somatostatin binding sites identified in control Jurkat cells (Ki1 = 78 +/- 3 pM and Ki2 = 12 +/- 4 nM [mean +/- SEM]; n = 4) was also observed. Almost identical results were obtained for phytohemagglutinin-activated human PBMC. In the absence of MV infection, two somatostatin binding sites were present (Ki1 = 111 +/- 31 pM and Ki2 = 17 +/- 2 nM [mean +/- SEM]; n = 2), whereas in MV-infected cells, only the high-affinity (Ki1 = 48 +/- 15 pM [mean +/- SEM]; n = 2) binding site remained. In addition, MV infection reinforced the inhibitory effects of SRIF on adenylyl cyclase activity, since maximal inhibition at 1 microM peptide was 11% +/- 4% in control cells versus 25% +/- 3% (P < 0.05) in infected Jurkat cells. Moreover, MV infection severely impaired the capacity of adenylyl cyclase to be activated directly (by forskolin) or indirectly (via Gs protein-coupled vasoactive intestinal peptide receptor). An assessment of [methyl-3H]thymidine incorporation showed that SRIF increased proliferative responses to mitogens only in control cells, not in MV-infected cells. Altogether, our data emphasize that MV-associated alteration of SRIF transduction appears to be related to the loss of SRIF-dependent increase of mitogen-induced proliferation.
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire, UMR49, Ecole Normale Supérieure, Lyon, France.
authors.forename: S
authors.initials: S
authors.lastname: Krantic
authors.forename: A
authors.initials: A
authors.lastname: Enjalbert
authors.forename: C
authors.initials: C
authors.lastname: Rabourdin-Combe
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D002462:Cell Membrane / Q000502:physiology / Q000821:virology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000201:enzymology; D015536:Down-Regulation; D006801:Humans; D007457:Iodine Radioisotopes; D019169:Jurkat Cells / Q000502:physiology / Q000821:virology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008459:Measles virus / Q000502:physiology*; D011869:Radioligand Assay; D017481:Receptors, Somatostatin / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D013004:Somatostatin / Q000378:metabolism / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology* / Q000821:virology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
chemical_list: D007457:Iodine Radioisotopes; D017481:Receptors, Somatostatin; D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D000262:Adenylyl Cyclases