The synthetic peptide WKYMVm attenuates the function of the chemokine receptors CCR5 and CXCR4 through activation of formyl peptide receptor-like 1. Export

@article{citeulike:3065667, abstract = {The G protein-coupled 7 transmembrane (STM) chemoattractant receptors can be inactivated by heterologous desensitization. Earlier work showed that formly peptide receptor-like 1 (FPRL1), an STM receptor with low affinity for the bacterial chemotactic peptide formyl-methionyl-leucyl-phenylalamine (fMLF), is activated by peptide domains derived from the human immunodeficiency virus (HIV)-1 envelope glycoprotein gp120 and its activation results in desensitization and down-regulation of the chemokine receptors CCR5 and CXCR4 from monocyte surfaces. This study investigated the possibility of interfering with the function of CCR5 or CXCR4 as HIV-1 coreceptors by activating FPRL1. Cell lines were established expressing FPRL1 in combination with CD4/CXCR4 or CD4/CCR5 and the effect of a synthetic peptide, WKYMVm, a potent activator of formyl peptide receptors with preference for FPRL1 was determined. Both CXCR4 and CCR5 were desensitized by activation of the cells with WKYMVm via a staurosporine-sensitive pathway. This desensitization of CXCR4 and CCR5 also attenuated their capacity as the fusion cofactors for HIV-1 envelope glycoprotein and resulted in a significant inhibition of p24 production by cell lines infected with HIV-1 that use CCR5 or CXCR4 as coreceptors. Furthermore, WKYMVm inhibited the infection of human peripheral monocyte-derived macrophages and CD4(+) T lymphocytes by R5 or X4 strains of HIV-1, respectively. These results indicate that heterologous desensitization of CCR5 and CXCR4 by an FPRL1 agonist attenuates their major biologic functions and suggest an approach to the development of additional anti-HIV-1 agents. (Blood. 2001;97:2941-2947)}, address = {Intramural Research Support Program and the Laboratory of Antiviral Drug Mechanism, NCI-Screening Technologies Branch, SAIC Frederick, MD, USA.}, author = {Li, B. Q. and Wetzel, M. A. and Mikovits, J. A. and Henderson, E. E. and Rogers, T. J. and Gong, W. and Le, Y. and Ruscetti, F. W. and Wang, J. M.}, citeulike-article-id = {3065667}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/11342415}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=11342415}, day = {15}, issn = {0006-4971}, journal = {Blood}, keywords = {ccr5}, month = {May}, number = {10}, pages = {2941--2947}, posted-at = {2008-07-31 15:43:15}, priority = {2}, title = {The synthetic peptide WKYMVm attenuates the function of the chemokine receptors CCR5 and CXCR4 through activation of formyl peptide receptor-like 1.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/11342415}, volume = {97}, year = {2001} }

TY - JOUR ID - citeulike:3065667 L3 - citeulike-article-id:3065667 N2 - The G protein-coupled 7 transmembrane (STM) chemoattractant receptors can be inactivated by heterologous desensitization. Earlier work showed that formly peptide receptor-like 1 (FPRL1), an STM receptor with low affinity for the bacterial chemotactic peptide formyl-methionyl-leucyl-phenylalamine (fMLF), is activated by peptide domains derived from the human immunodeficiency virus (HIV)-1 envelope glycoprotein gp120 and its activation results in desensitization and down-regulation of the chemokine receptors CCR5 and CXCR4 from monocyte surfaces. This study investigated the possibility of interfering with the function of CCR5 or CXCR4 as HIV-1 coreceptors by activating FPRL1. Cell lines were established expressing FPRL1 in combination with CD4/CXCR4 or CD4/CCR5 and the effect of a synthetic peptide, WKYMVm, a potent activator of formyl peptide receptors with preference for FPRL1 was determined. Both CXCR4 and CCR5 were desensitized by activation of the cells with WKYMVm via a staurosporine-sensitive pathway. This desensitization of CXCR4 and CCR5 also attenuated their capacity as the fusion cofactors for HIV-1 envelope glycoprotein and resulted in a significant inhibition of p24 production by cell lines infected with HIV-1 that use CCR5 or CXCR4 as coreceptors. Furthermore, WKYMVm inhibited the infection of human peripheral monocyte-derived macrophages and CD4(+) T lymphocytes by R5 or X4 strains of HIV-1, respectively. These results indicate that heterologous desensitization of CCR5 and CXCR4 by an FPRL1 agonist attenuates their major biologic functions and suggest an approach to the development of additional anti-HIV-1 agents. (Blood. 2001;97:2941-2947) IS - 10 JF - Blood SN - 0006-4971 AD - Intramural Research Support Program and the Laboratory of Antiviral Drug Mechanism, NCI-Screening Technologies Branch, SAIC Frederick, MD, USA. EP - 2947 TI - The synthetic peptide WKYMVm attenuates the function of the chemokine receptors CCR5 and CXCR4 through activation of formyl peptide receptor-like 1. VL - 97 SP - 2941 KW - ccr5 AU - Li, BQ AU - Wetzel, MA AU - Mikovits, JA AU - Henderson, EE AU - Rogers, TJ AU - Gong, W AU - Le, Y AU - Ruscetti, FW AU - Wang, JM PY - 2001/05/15/ UR - http://view.ncbi.nlm.nih.gov/pubmed/11342415 ER -