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dc.contributor.authorCaccuri, Francesca
dc.contributor.authorD'Ursi, Pasqualina
dc.contributor.authorUggeri, Matteo
dc.contributor.authorBugatti, Antonella
dc.contributor.authorMazzuca, Pietro
dc.contributor.authorZani, Alberto
dc.contributor.authorFilippini, Federica
dc.contributor.authorSalmona, Mario
dc.contributor.authorRibatti, Domenico
dc.contributor.authorSlevin, Mark
dc.contributor.authorOrro, Alessandro
dc.contributor.authorLu, Wuyuan
dc.contributor.authorLiò, Pietro
dc.contributor.authorGallo, Robert C
dc.contributor.authorCaruso, Arnaldo
dc.date.accessioned2021-01-15T21:28:58Z
dc.date.available2021-01-15T21:28:58Z
dc.identifier.urihttp://hdl.handle.net/10713/14359
dc.description.abstractThe 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.en_US
dc.description.urihttps://doi.org/10.1073/pnas.2021366118en_US
dc.language.isoenen_US
dc.publisherNational Academy of Sciences of the United States of Americaen_US
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.rightsCopyright © 2021 the Author(s). Published by PNAS.en_US
dc.subjectHIV-1 and HIV-2 ancestorsen_US
dc.subjectHIV-1 evolutionary trajectoryen_US
dc.subjectHIV-1 matrix protein p17en_US
dc.subjectcommon beta chain receptoren_US
dc.subjecthuman erythropoietinen_US
dc.titleEvolution toward beta common chain receptor usage links the matrix proteins of HIV-1 and its ancestors to human erythropoietin.en_US
dc.typeArticleen_US
dc.identifier.doi10.1073/pnas.2021366118
dc.identifier.pmid33372148
dc.source.volume118
dc.source.issue2
dc.source.countryUnited States


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