Interleukin-8-mediated Heterologous Receptor Internalization Provides Resistance to HIV-1 Infectivity. ROLE OF SIGNAL STRENGTH AND RECEPTOR DESENSITIZATION Export

@article{citeulike:2871636, abstract = {Human immunodeficiency virus type 1 (HIV-1) entry into CD4+ cells requires the chemokine receptors CCR5 or CXCR4 as co-fusion receptors. We have previously demonstrated that chemokine receptors are capable of cross-regulating the functions of each other and, thus, affecting cellular responsiveness at the site of infection. To investigate the effects of chemokine receptor cross-regulation in HIV-1 infection, monocytes and MAGIC5 and rat basophilic leukemia (RBL-2H3) cell lines co-expressing the interleukin-8 (IL-8 or CXCL8) receptor CXCR1 and either CCR5 (ACCR5) or CXCR4 (ACXCR4) were generated. IL-8 activation of CXCR1, but not the IL-8 receptor CXCR2, cross-phosphorylated CCR5 and CXCR4 and cross-desensitized their responsiveness to RANTES (regulated on activation normal T cell expressed and secreted) (CCL5) and stromal derived factor (SDF-1 or CXCL12), respectively. CXCR1 activation internalized CCR5 but not CXCR4 despite cross-phosphorylation of both. IL-8 pretreatment also inhibited CCR5- but not CXCR4-mediated virus entry into MAGIC5 cells. A tail-deleted mutant of CXCR1, [Delta]CXCR1, produced greater signals upon activation (Ca2+ mobilization and phosphoinositide hydrolysis) and cross-internalized CXCR4, inhibiting HIV-1 entry. The protein kinase C inhibitor staurosporine prevented phosphorylation and internalization of the receptors by CXCR1 activation. Taken together, these results indicate that chemokine receptor-mediated HIV-1 cell infection is blocked by receptor internalization but not desensitization alone. Thus, activation of chemokine receptors unrelated to CCR5 and CXCR4 may play a cross-regulatory role in the infection and propagation of HIV-1. Since [Delta]CXCR1, but not CXCR1, cross-internalized and cross-inhibited HIV-1 infection to CXCR4, the data indicate the importance of the signal strength of a receptor and, as a consequence, protein kinase C activation in the suppression of HIV-1 infection by cross-receptor-mediated internalization. 10.1074/jbc.M211745200}, author = {Richardson, Ricardo M. and Tokunaga, Kenzo and Marjoram, Robin and Sata, Tetsutaro and Snyderman, Ralph}, citeulike-article-id = {2871636}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M211745200}, citeulike-linkout-1 = {http://www.jbc.org/cgi/content/abstract/278/18/15867}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/12594210}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=12594210}, day = {25}, doi = {10.1074/jbc.M211745200}, journal = {J. Biol. Chem.}, keywords = {ccr5, endocytosis, hiv}, month = {April}, number = {18}, pages = {15867--15873}, posted-at = {2008-06-07 16:07:57}, priority = {2}, title = {Interleukin-8-mediated Heterologous Receptor Internalization Provides Resistance to HIV-1 Infectivity. ROLE OF SIGNAL STRENGTH AND RECEPTOR DESENSITIZATION}, url = {http://dx.doi.org/10.1074/jbc.M211745200}, volume = {278}, year = {2003} }

TY - JOUR ID - citeulike:2871636 L3 - citeulike-article-id:2871636 N2 - Human immunodeficiency virus type 1 (HIV-1) entry into CD4+ cells requires the chemokine receptors CCR5 or CXCR4 as co-fusion receptors. We have previously demonstrated that chemokine receptors are capable of cross-regulating the functions of each other and, thus, affecting cellular responsiveness at the site of infection. To investigate the effects of chemokine receptor cross-regulation in HIV-1 infection, monocytes and MAGIC5 and rat basophilic leukemia (RBL-2H3) cell lines co-expressing the interleukin-8 (IL-8 or CXCL8) receptor CXCR1 and either CCR5 (ACCR5) or CXCR4 (ACXCR4) were generated. IL-8 activation of CXCR1, but not the IL-8 receptor CXCR2, cross-phosphorylated CCR5 and CXCR4 and cross-desensitized their responsiveness to RANTES (regulated on activation normal T cell expressed and secreted) (CCL5) and stromal derived factor (SDF-1 or CXCL12), respectively. CXCR1 activation internalized CCR5 but not CXCR4 despite cross-phosphorylation of both. IL-8 pretreatment also inhibited CCR5- but not CXCR4-mediated virus entry into MAGIC5 cells. A tail-deleted mutant of CXCR1, [Delta]CXCR1, produced greater signals upon activation (Ca2+ mobilization and phosphoinositide hydrolysis) and cross-internalized CXCR4, inhibiting HIV-1 entry. The protein kinase C inhibitor staurosporine prevented phosphorylation and internalization of the receptors by CXCR1 activation. Taken together, these results indicate that chemokine receptor-mediated HIV-1 cell infection is blocked by receptor internalization but not desensitization alone. Thus, activation of chemokine receptors unrelated to CCR5 and CXCR4 may play a cross-regulatory role in the infection and propagation of HIV-1. Since [Delta]CXCR1, but not CXCR1, cross-internalized and cross-inhibited HIV-1 infection to CXCR4, the data indicate the importance of the signal strength of a receptor and, as a consequence, protein kinase C activation in the suppression of HIV-1 infection by cross-receptor-mediated internalization. 10.1074/jbc.M211745200 IS - 18 JF - J. Biol. Chem. EP - 15873 TI - Interleukin-8-mediated Heterologous Receptor Internalization Provides Resistance to HIV-1 Infectivity. ROLE OF SIGNAL STRENGTH AND RECEPTOR DESENSITIZATION VL - 278 SP - 15867 KW - ccr5 KW - endocytosis KW - hiv AU - Richardson, Ricardo AU - Tokunaga, Kenzo AU - Marjoram, Robin AU - Sata, Tetsutaro AU - Snyderman, Ralph PY - 2003/04/25/ UR - http://dx.doi.org/10.1074/jbc.M211745200 ER -