Evolution toward beta common chain receptor usage links the matrix proteins of HIV-1 and its ancestors to human erythropoietin.
Author
Caccuri, FrancescaD'Ursi, Pasqualina
Uggeri, Matteo
Bugatti, Antonella
Mazzuca, Pietro
Zani, Alberto
Filippini, Federica
Salmona, Mario
Ribatti, Domenico
Slevin, Mark
Orro, Alessandro
Lu, Wuyuan
Liò, Pietro
Gallo, Robert C
Caruso, Arnaldo
Journal
Proceedings of the National Academy of Sciences of the United States of AmericaPublisher
National Academy of Sciences of the United States of AmericaType
Article
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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.Rights/Terms
Copyright © 2021 the Author(s). Published by PNAS.Keyword
HIV-1 and HIV-2 ancestorsHIV-1 evolutionary trajectory
HIV-1 matrix protein p17
common beta chain receptor
human erythropoietin
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http://hdl.handle.net/10713/14359ae974a485f413a2113503eed53cd6c53
10.1073/pnas.2021366118
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