气候变化领域集成服务门户(CCPortal): Natural cystatin C fragments inhibit GPR15-mediated HIV and SIV infection without interfering with GPR15L signaling

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DOI	10.1073/pnas.2023776118
	Natural cystatin C fragments inhibit GPR15-mediated HIV and SIV infection without interfering with GPR15L signaling
	Hayn M.; Blötz A.; Rodríguez A.; Vidal S.; Preising N.; Ständker L.; Wiese S.; Stürzel C.M.; Harms M.; Gross R.; Jung C.; Kiene M.; Jacob T.; Pöhlmann S.; Forssmann W.-G.; Münch J.; Sparrer K.M.J.; Seuwen K.; Hahn B.H.; Kirchhoff F.
发表日期	2021
ISSN	00278424
卷号	118 期号:3
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	G protein-coupled receptors \| GPR15 \| immunodeficiency viruses \| chemokines \| cystatin C
语种	英语
scopus关键词	chemokine receptor CXCR7; cystatin C; ligand; proteinase; antiviral activity; Article; carboxy terminal sequence; CD4+ T lymphocyte; controlled study; enzyme activation; human; human cell; Human immunodeficiency virus 1 infection; Human immunodeficiency virus 2 infection; inflammation; nonhuman; peptide library; priority journal; protein analysis; protein binding; protein degradation; protein function; signal transduction; simian acquired immunodeficiency syndrome; virus cell interaction; virus entry
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181002
作者单位	Institute of Molecular Virology, Ulm University Medical Center, Ulm, 89081, Germany; Core Facility Functional Peptidomics, Ulm University Medical Center, Ulm, 89081, Germany; Core Unit Mass Spectrometry and Proteomics, Ulm University Medical Center, Ulm, 89081, Germany; PHARIS Biotec GmbH, Hannover, 30625, Germany; Novartis Institutes for Biomedical Research, Basel, 4056, Switzerland; Institute of Electrochemistry, Ulm University, Ulm, 89081, Germany; Infection Biology Unit, German Primate Center–Leibniz Institute for Primate Research, Göttingen, 37077, Germany; Faculty of Biology and Psychology, University Göttingen, Göttingen, 37073, Germany; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6076, United States; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6076, United States
推荐引用方式 GB/T 7714	Hayn M.,Blötz A.,Rodríguez A.,et al. Natural cystatin C fragments inhibit GPR15-mediated HIV and SIV infection without interfering with GPR15L signaling[J],2021,118(3).
APA	Hayn M..,Blötz A..,Rodríguez A..,Vidal S..,Preising N..,...&Kirchhoff F..(2021).Natural cystatin C fragments inhibit GPR15-mediated HIV and SIV infection without interfering with GPR15L signaling.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA	Hayn M.,et al."Natural cystatin C fragments inhibit GPR15-mediated HIV and SIV infection without interfering with GPR15L signaling".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).