气候变化领域集成服务门户(CCPortal): Evolution toward beta common chain receptor usage links the matrix proteins of HIV-1 and its ancestors to human erythropoietin

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DOI	10.1073/pnas.2021366118
	Evolution toward beta common chain receptor usage links the matrix proteins of HIV-1 and its ancestors to human erythropoietin
	Caccuri F.; D'Ursi P.; Uggeri M.; Bugatti A.; Mazzuca P.; Zani A.; Filippini F.; Salmona M.; Ribatti D.; Slevin M.; Orro A.; Lu W.; Liò P.; Gallo R.C.; Caruso A.
发表日期	2021
ISSN	00278424
卷号	118 期号:2
英文摘要	The HIV-1 matrix protein p17 (p17) is a pleiotropic molecule impacting on different cell types. Its interaction with many cellular proteins underlines the importance of the viral protein as a major determinant of human specific adaptation. We previously showed the proangiogenic capability of p17. Here, by integrating functional analysis and receptor binding, we identify a functional epitope that displays molecular mimicry with human erythropoietin (EPO) and promotes angiogenesis through common beta chain receptor (βCR) activation. The functional EPO-like epitope was found to be present in the matrix protein of HIV-1 ancestors SIV originated in chimpanzees (SIVcpz) and gorillas (SIVgor) but not in that of HIV-2 and its ancestor SIVsmm from sooty mangabeys. According to biological data, evolution of the EPO-like epitope showed a clear differentiation between HIV-1/SIVcpz-gor and HIV-2/SIVsmm branches, thus highlighting this epitope on p17 as a divergent signature discriminating HIV-1 and HIV-2 ancestors. P17 is known to enhance HIV-1 replication. Similarly to other βCR ligands, p17 is capable of attracting and activating HIV-1 target cells and promoting a proinflammatory microenvironment. Thus, it is tempting to speculate that acquisition of an epitope on the matrix proteins of HIV-1 ancestors capable of triggering βCR may have represented a critical step to enhance viral aggressiveness and early human-to-human SIVcpz/gor dissemination. The hypothesis that the p17/βCR interaction and βCR abnormal stimulation may also play a role in sustaining chronic activation and inflammation, thus marking the difference between HIV-1 and HIV-2 in term of pathogenicity, needs further investigation. © This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
英文关键词	Common beta chain receptor; HIV-1 and HIV-2 ancestors; HIV-1 evolutionary trajectory; HIV-1 matrix protein p17; Human erythropoietin
语种	英语
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/181030
作者单位	Department of Molecular and Translational Medicine, University of Brescia, Medical School, Brescia, 25123, Italy; Institute of Technologies in Biomedicine, National Research Council, Segrate, 20090, Italy; Department of Pharmacy, University of Genova, Genova, 16132, Italy; Istituti di Ricovero e Cura a Carattere Assistenziale Istituto di Ricerche Farmacologiche Mario Negri, Milan, 20156, Italy; Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari, Medical School, Bari, 70124, Italy; School of Healthcare Science, Manchester Metropolitan University, Manchester, M15GD, United Kingdom; Institute of Human Virology, University of Maryland, Baltimore, MD 21201, United States; Department of Computer Science and Technology, University of Cambridge, Cambridge, CB3 0FD, United Kingdom
推荐引用方式 GB/T 7714	Caccuri F.,D'Ursi P.,Uggeri M.,et al. Evolution toward beta common chain receptor usage links the matrix proteins of HIV-1 and its ancestors to human erythropoietin[J],2021,118(2).
APA	Caccuri F..,D'Ursi P..,Uggeri M..,Bugatti A..,Mazzuca P..,...&Caruso A..(2021).Evolution toward beta common chain receptor usage links the matrix proteins of HIV-1 and its ancestors to human erythropoietin.Proceedings of the National Academy of Sciences of the United States of America,118(2).
MLA	Caccuri F.,et al."Evolution toward beta common chain receptor usage links the matrix proteins of HIV-1 and its ancestors to human erythropoietin".Proceedings of the National Academy of Sciences of the United States of America 118.2(2021).