MEASLES-VIRUS MODULATES HUMAN T-CELL SOMATOSTATIN RECEPTORS AND THEIRCOUPLING TO ADENYLYL-CYCLASE

The possible role of immunomodulatory peptide somatostatin (SRIF) in m easles virus (MV)-induced immunopathology was addressed by analysis of SRIF receptors and their coupling to adenylyl cyclase in mitogen-stim ulated Jurkat T cells and human peripheral blood mononuclear cells (PB MC). SRIF-specific receptors were assayed in semipurified membrane pre parations by using SRIF14 containing iodinated tyrosine at the first p osition in the amino acid chain ([I-125]Tyr(1)) as a radioligand. A de termination of receptor number by saturation of radioligand binding at equilibrium showed that in Jurkat cells, MV infection led to a dramat ic decrease in the total receptor number, The virus-associated disappe arance of one (K-i2 = 12 +/- 4 nhl [mean a standard error of the mean {SEM}] n = 4) of two somatostatin binding sites identified in control Jurkat cells (K-i1 = 78 +/- 3 pM and K-i2 = 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 infectio n, two somatostatin binding sites were present (K-i1 = 111 +/- 31 pM a nd K-i2 = 17 +/- 2 nM [mean +/- SEM]; n = 2)1 whereas in MV-infected c ells, only the high-affinity. (K-i1 = 48 +/- 15 pM [mean +/- SEM]; n = 2) binding site remained, In addition, MV infection reinforced the in hibitory effects of SRIF on adenylyl cyclase activity since maximal in hibition at 1 mu M peptide was 11% +/- 4% in control cells versus 25% +/- 3% (P < 0.05) in infected Jurkat cells, Moreover, MV infection sev erely impaired the capacity of adenylyl cyclase to be activated direct ly (by forskolin) or indirectly (via Gs protein-coupled vasoactive int estinal peptide receptor), An assessment of [methyl-H-3]thy-midine inc orporation showed that SRIF increased proliferative responses to mitog ens only in control cells, not in MV-infected cells, Altogether, our d ata emphasize that MV-associated alteration of SRIF transduction appea rs to be related to the loss of SRIF-dependent increase of mitogen-ind uced proliferation.