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Viruses 2018, 10(1), 9; doi:10.3390/v10010009

The Abrogation of Phosphorylation Plays a Relevant Role in the CCR5 Signalosome Formation with Natural Antibodies to CCR5

1
Division of Immunology, Transplantation and Infectious Diseases, DIBIT-San Raffaele Scientific Institute, 20132 Milan, Italy
2
Infections and Cancer Biology Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon CEDEX 08, France
3
Department of Chemical Biological Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
4
Third Division of Infectious Diseases, Luigi Sacco Hospital, University of Milan, 20157 Milan, Italy
*
Author to whom correspondence should be addressed.
Received: 5 December 2017 / Revised: 21 December 2017 / Accepted: 25 December 2017 / Published: 28 December 2017
(This article belongs to the Section Antivirals & Vaccines)
View Full-Text   |   Download PDF [3269 KB, uploaded 28 December 2017]   |  

Abstract

The exposure to CCR5 (CC chemokine receptor 5) specific natural antibodies in vitro produces a Class B β-arrestin2-dependent CCR5 retention with the aid of ERK1, due to the formation of a CCR5 signalosome, which remains stable for at least 48 h. Considering that β-arrestins and MAPKs are receptive to environmental signals, their signal complexes could be one of the key junction for GPCRs internalization related signal transduction. Here, we demonstrate that, in T cells, the phosphorylation status of either CCR5 receptor or ERK1 protein is necessary to drive the internalized receptor into the early endosomes, forming the CCR5 signalosome. In particular, our data show that β-arrestin2/ERK1 complex is a relevant transducer in the CCR5 signaling pathway. Understanding the mechanism of CCR5 regulation is essential for many inflammatory disorders, tumorigenesis and viral infection such as HIV. View Full-Text
Keywords: CCR5; anti CCR5 antibodies; CCR5 signalosome; HIV infection; HIV protection; CCR5 based therapy; ESN; LTNP CCR5; anti CCR5 antibodies; CCR5 signalosome; HIV infection; HIV protection; CCR5 based therapy; ESN; LTNP
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Venuti, A.; Pastori, C.; Siracusano, G.; Pennisi, R.; Riva, A.; Tommasino, M.; Sciortino, M.T.; Lopalco, L. The Abrogation of Phosphorylation Plays a Relevant Role in the CCR5 Signalosome Formation with Natural Antibodies to CCR5. Viruses 2018, 10, 9.

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