scholarly journals Natural Cystatin C fragments inhibit GPR15-mediated HIV and SIV infection without interfering with GPR15L signaling

2020 ◽  
Author(s):  
Manuel Hayn ◽  
Andrea Blötz ◽  
Armando Rodríguez ◽  
Solange Vidal ◽  
Nico Preising ◽  
...  
Keyword(s):  
G Protein ◽  
Cystatin C ◽  
Viral Entry ◽  
Physiological Function ◽  
G Protein Coupled Receptor ◽  
Chemokine Ligand ◽  
Siv Infection ◽  
G Protein Coupled ◽  
Hiv 1 ◽  
Antiretroviral Activity

SUMMARYGPR15 is a G protein-coupled receptor proposed to play a role in mucosal immunity that also serves as entry cofactor for HIV and SIV. To discover novel endogenous GPR15 ligands, we screened a hemofiltrate-derived peptide library for inhibitors of GPR15-mediated SIV infection. Our approach identified a C-terminal fragment of Cystatin C (CysC95-146) that specifically inhibits GPR15-dependent HIV-1, HIV-2 and SIV infection. In contrast, GPR15L, the chemokine ligand of GPR15, failed to inhibit virus infection. We found that Cystatin C fragments preventing GPR15-mediated viral entry do not interfere with GPR15L signaling and are generated by proteases activated at sites of inflammation. The antiretroviral activity of CysC95-146 was confirmed in primary CD4+ T cells and is conserved in simian hosts of SIV infection. Thus, we identified a potent endogenous inhibitor of GPR15-mediated HIV and SIV infection that does not interfere with the physiological function of this G protein-coupled receptor.

scholarly journals Natural cystatin C fragments inhibit GPR15-mediated HIV and SIV infection without interfering with GPR15L signaling

2021 ◽  
Vol 118 (3) ◽  
pp. e2023776118
Author(s):  
Manuel Hayn ◽  
Andrea Blötz ◽  
Armando Rodríguez ◽  
Solange Vidal ◽  
Nico Preising ◽  
...  
Keyword(s):  
Cystatin C ◽  
Viral Entry ◽  
Physiological Function ◽  
Endogenous Inhibitor ◽  
Immunodeficiency Virus ◽  
Chemokine Ligand ◽  
Siv Infection ◽  
G Protein Coupled ◽  
Hiv 1 ◽  
Antiretroviral Activity

GPR15 is a G protein-coupled receptor (GPCR) proposed to play a role in mucosal immunity that also serves as a major entry cofactor for HIV-2 and simian immunodeficiency virus (SIV). To discover novel endogenous GPR15 ligands, we screened a hemofiltrate (HF)-derived peptide library for inhibitors of GPR15-mediated SIV infection. Our approach identified a C-terminal fragment of cystatin C (CysC95-146) that specifically inhibits GPR15-dependent HIV-1, HIV-2, and SIV infection. In contrast, GPR15L, the chemokine ligand of GPR15, failed to inhibit virus infection. We found that cystatin C fragments preventing GPR15-mediated viral entry do not interfere with GPR15L signaling and are generated by proteases activated at sites of inflammation. The antiretroviral activity of CysC95-146 was confirmed in primary CD4+ T cells and is conserved in simian hosts of SIV infection. Thus, we identified a potent endogenous inhibitor of GPR15-mediated HIV and SIV infection that does not interfere with the physiological function of this GPCR.

scholarly journals The Synthetic Peptide Derived from the NH2-terminal Extracellular Region of an Orphan G Protein-coupled Receptor, GPR1, Preferentially Inhibits Infection of X4 HIV-1

2005 ◽  
Vol 280 (35) ◽  
pp. 30924-30934 ◽  
Author(s):  
Atsushi Jinno-Oue ◽  
Nobuaki Shimizu ◽  
Yasushi Soda ◽  
Atsushi Tanaka ◽  
Takahiro Ohtsuki ◽  
...  
Keyword(s):  
G Protein ◽  
Synthetic Peptide ◽  
G Protein Coupled Receptor ◽  
Extracellular Region ◽  
G Protein Coupled ◽  
Hiv 1

scholarly journals An activator of G protein-coupled receptor and MEK1/2-ERK1/2 signaling inhibits HIV-1 replication by altering viral RNA processing

2020 ◽  
Vol 16 (2) ◽  
pp. e1008307 ◽  
Author(s):  
Raymond W. Wong ◽  
Ahalya Balachandran ◽  
Peter K. Cheung ◽  
Ran Cheng ◽  
Qun Pan ◽  
...  
Keyword(s):  
G Protein ◽  
Rna Processing ◽  
Viral Rna ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled ◽  
Hiv 1

scholarly journals Dynamic conformational switching in the chemokine ligand is essential for G-protein-coupled receptor activation

2013 ◽  
Vol 456 (2) ◽  
pp. 241-251 ◽  
Author(s):  
Prem Raj B. Joseph ◽  
Kirti V. Sawant ◽  
Angela Isley ◽  
Mesias Pedroza ◽  
Roberto P. Garofalo ◽  
...  
Keyword(s):  
G Protein ◽  
Receptor Activation ◽  
G Protein Coupled Receptor ◽  
Conformational Switching ◽  
Conformational Substates ◽  
Chemokine Ligand ◽  
G Protein Coupled ◽  
Terminal Site ◽  
Multiple Receptor

How chemokine N-loop (Site-I) and N-terminal (Site-II) residues activate multiple receptor activities in neutrophils is not known. We show in CXCL8, a distally located Gly-Pro motif couples Site-I and Site-II, and propose that such coupling dictates the conformational substates for various functions.

scholarly journals An Orphan G Protein-Coupled Receptor, GPR1, Acts as a Coreceptor To Allow Replication of Human Immunodeficiency Virus Types 1 and 2 in Brain-Derived Cells

1999 ◽  
Vol 73 (6) ◽  
pp. 5231-5239 ◽  
Author(s):  
Nobuaki Shimizu ◽  
Yasushi Soda ◽  
Katsuaki Kanbe ◽  
Hui-Yu Liu ◽  
Atsushi Jinno ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Line ◽  
G Protein ◽  
Chemokine Receptors ◽  
Single Point ◽  
G Protein Coupled Receptor ◽  
Immunodeficiency Virus ◽  
G Protein Coupled ◽  
Hiv 1

ABSTRACT Twelve G protein-coupled receptors, including chemokine receptors, act as coreceptors and determinants for the cell tropisms of human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus (SIV). We isolated HIV-1 variants from T-cell-line (T)- and macrophage (M)-tropic (i.e., dualtropic) (R5-R3-X4) HIV-1 strains and also produced six HIV-1 mutants carrying single-point amino acid substitutions at the tip of the V3 region of the Env protein of HIV-1. These variants and three mutants infected brain-derived CD4-positive cells that are resistant to M-, T-, or dualtropic (R5, X4, or R5-X4) HIV-1 strains. However, a factor that determines this cell tropism has not been identified. This study shows that primary brain-derived fibroblast-like cell strains, BT-3 and BT-20/N, as well as a CD4-transduced glioma cell line, U87/CD4, which were susceptible to these HIV-1 variants and mutants and the HIV-2ROD strain, expressed mRNA of an orphan G protein-coupled receptor (GPCR), GPR1. When a CD4-positive cell line which was strictly resistant to infection with diverse HIV-1 and HIV-2 strains was transduced with GPR1, the cell line became susceptible to these HIV-1 variants and mutants and to an HIV-2 strain but not to T- or dualtropic HIV-1 strains, and numerous syncytia formed after infection. These results indicate that GPR1 functions as a coreceptor for the HIV-1 variants and mutants and for the HIV-2ROD strain in vitro.

HIV-1 Entry Cofactor: Functional cDNA Cloning of a Seven-Transmembrane, G Protein-Coupled Receptor

Science ◽  
1996 ◽  
Vol 272 (5263) ◽  
pp. 872-877 ◽  
Author(s):  
Y. Feng ◽  
C. C. Broder ◽  
P. E. Kennedy ◽  
E. A. Berger
Keyword(s):  
G Protein ◽  
Cdna Cloning ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled ◽  
Hiv 1

scholarly journals Mikst Orjinli Köpek Meme Tümörlerinde CXC Chemokine Ligand 12 ve G Protein Coupled Receptor 30 Ekspresyonları

2018 ◽  
Vol 11 (2) ◽  
pp. 1-2 ◽  
Author(s):  
Mehmet Eray ALÇIĞIR ◽  
Elvan ANADOL ◽  
Nilgün GÜLTİKEN ◽  
Kübra KARAKAŞ ALKAN ◽  
Hasan ALKAN ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptor ◽  
Cxc Chemokine ◽  
Chemokine Ligand ◽  
G Protein Coupled
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