B-cell clonogenic activity of HIV-1 p17 variants is driven by PAR1-mediated EGF transactivation [* Cross-Reference *]

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Cinzia Giagulli; Francesca Caccuri; Simone Zorzan; Antonella Bugatti; Alberto Zani; Federica Filippini; Ekta Manocha; Pasqualina D’Ursi; Alessandro Orro; Riccardo Dolcetti; Arnaldo Caruso, 2026, "B-cell clonogenic activity of HIV-1 p17 variants is driven by PAR1-mediated EGF transactivation [* Cross-Reference *]", https://lore.list.lu/citation?persistentId=perma:LIST.8BBDHQ, LIST Open Repository, V1
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Description
Combined antiretroviral therapy (cART) for HIV-1 dramatically slows disease progression among HIV+ individuals. Currently, lymphoma represents the main cause of death among HIV-1-infected patients. Detection of p17 variants (vp17s) endowed with B-cell clonogenic activity in HIV-1-seropositive patients with lymphoma suggests their possible role in lymphomagenesis. Here, we demonstrate that the clonogenic activity of vp17s is mediated by their binding to PAR1 and to PAR1-mediated EGFR transactivation through Gq protein. The entire vp17s-triggered clonogenic process is MMPs dependent. Moreover, phosphoproteomic and bioinformatic analysis highlighted the crucial role of EGFR/PI3K/Akt pathway in modulating several molecules promoting cancer progression, including RAC1, ABL1, p53, CDK1, NPM, Rb, PTP-1B, and STAT1. Finally, we show that a peptide (F1) corresponding to the vp17s functional epitope is sufficient to trigger the PAR1/EGFR/PI3K/Akt pathway and bind PAR1. Our findings suggest novel potential therapeutic targets to counteract vp17-driven lymphomagenesis in HIV+ patients. (2020-10-22)
***This entry has been automatically imported via OpenAlex by LIST harvest scripts. Please refer to https://doi.org/10.1038/s41417-020-00246-9 for the original and latest version of the publication*** (2026-07-01)
Subject Medicine, Health and Life Sciences
Keyword Transactivation, Clonogenic assay, Cancer research, Protein kinase B, PI3K/AKT/mTOR pathway, Biology, Epitope, Signal transduction, Cell, Immunology, Cell biology, Transcription factor, Antibody, Gene, Genetics
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