{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T16:44:49Z","timestamp":1775321089647,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T00:00:00Z","timestamp":1719532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007076","name":"Associazione Italiana per la Ricerca sul Cancro (AIRC) to Arnaldo Caruso","doi-asserted-by":"publisher","award":["20108"],"award-info":[{"award-number":["20108"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Associazione Italiana per la Ricerca sul Cancro (AIRC) to Arnaldo Caruso","doi-asserted-by":"publisher","award":["760252\/28.12.2023"],"award-info":[{"award-number":["760252\/28.12.2023"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"name":"PNRR\/2022\/C9\/MCID\/I8-Development of a program to attract highly specialized human resources from abroad in research, development, and innovation activities to Francesca Caccuri","award":["20108"],"award-info":[{"award-number":["20108"]}]},{"name":"PNRR\/2022\/C9\/MCID\/I8-Development of a program to attract highly specialized human resources from abroad in research, development, and innovation activities to Francesca Caccuri","award":["760252\/28.12.2023"],"award-info":[{"award-number":["760252\/28.12.2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The human immunodeficiency virus (HIV-1) matrix protein p17 (p17) is released from infected cells as a protein capable of deregulating the biological activity of different cells. P17 variants (vp17s), more frequently detected in the plasma of HIV-1+ patients with rather than without lymphoma and characterized by amino acids insertions in their C-terminal region, were found to trigger B cell growth and clonogenicity. Vp17s endowed with B-cell-growth-promoting activity are drastically destabilized, whereas, in a properly folded state, reference p17 (refp17) does not exert any biological activity on B cell growth and clonogenicity. However, misfolding of refp17 is necessary to expose a masked functional epitope, interacting with the protease-activated receptor 1 (PAR-1), endowed with B cell clonogenicity. Indeed, it is worth noting that changes in the secondary structure can strongly impact the function of a protein. Here, we performed computational studies to show that the gain of function of vp17s is linked to dramatic conformational changes due to structural modification in the secondary-structure elements and in the rearrangement of the hydrogen bond (H-bond) network. In particular, all clonogenic vp17s showed the disengagement of two critical residues, namely Trp16 and Tyr29, from their hydrophobic core. Biological data showed that the mutation of Trp16 and Tyr29 to Ala in the refp17 backbone, alone or in combination, resulted in a protein endowed with B cell clonogenic activity. These data show the pivotal role of the hydrophobic component in maintaining refp17 stability and identify a novel potential therapeutic target to counteract vp17-driven lymphomagenesis in HIV-1+ patients.<\/jats:p>","DOI":"10.3390\/v16071048","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T03:38:27Z","timestamp":1719805107000},"page":"1048","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Molecular Mechanisms Involved in the B Cell Growth and Clonogenic Activity of HIV-1 Matrix Protein p17 Variants"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1554-429X","authenticated-orcid":false,"given":"Pasqualina","family":"D\u2019Ursi","sequence":"first","affiliation":[{"name":"Institute of Technologies in Biomedicine, National Research Council, 20090 Segrate, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4718-5914","authenticated-orcid":false,"given":"Alessandro","family":"Rondina","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9066-7973","authenticated-orcid":false,"given":"Alberto","family":"Zani","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0429-2499","authenticated-orcid":false,"given":"Matteo","family":"Uggeri","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"},{"name":"Lifescience Innovation Good Healthcare Technology\u2014LIGHT s.c.ar.l., 25123 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Messali","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnaldo","family":"Caruso","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"},{"name":"Centre for Advanced Medical and Pharmaceutical Research, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science and Technology, 540142 Targu Mures, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1923-9033","authenticated-orcid":false,"given":"Francesca","family":"Caccuri","sequence":"additional","affiliation":[{"name":"Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"},{"name":"Centre for Advanced Medical and Pharmaceutical Research, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science and Technology, 540142 Targu Mures, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,28]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Functions of the HIV-1 matrix protein p17","volume":"29","author":"Fiorentini","year":"2006","journal-title":"New Microbiol."},{"key":"ref_2","first-page":"163","article-title":"HIV-1 infection, microenvironment and endothelial cell dysfunction","volume":"39","author":"Mazzuca","year":"2016","journal-title":"New Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"14807","DOI":"10.1073\/pnas.0506857102","article-title":"Persistence of HIV-1 structural proteins and glycoproteins in lymph nodes of patients under highly active antiretroviral therapy","volume":"102","author":"Popovic","year":"2005","journal-title":"Proc. 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