Abstract
Cross-desensitization between G protein-coupled receptors (GPCRs) can play an important role in the regulation of the immune response. Recent research shows that the receptor for nociceptin/orphanin FQ (N/OFQ), designated the orphan opioid receptor-like 1 (ORL1) exerts a significant effect on adaptive immunity. We carried out experiments to determine the capacity of ORL1 to desensitize the major HIV co-receptor CXCR4. Our results show that ORL1 induced significant desensitization of CXCR4 in both CD4-positive T cells and CD14-positive monocytes, as well as the CD4-positive Jurkat T cell, and U937 monocyte-like cell lines. In addition, the cross-desensitization of CXCR4 by ORL1 did not result in detectable internalization of CXCR4 in either primary cells or the hematopoietic cell lines. Finally, results show that the heterologous-desensitization of CXCR4 was associated with reduced susceptibility to HIV-1 infection. Given the relative resistance of CXCR4 to cross-desensitization, our studies suggest that ORL1 possesses a high level of regulatory activity.
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