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The possible pathogenic involvement of HIV p17 protein variants was investigated in a particularly informative case of HIV\u2010related splenic marginal zone lymphoma, which was negative for oncogenic virus infections, thus allowing us to assess the possible direct contribution of these HIV\u2010encoded proteins to lymphomagenesis. The presence of p17 protein was analyzed by immunohistochemistry in lymphoma tissue. Recombinant p17 protein derived from the dominant sequence detected in plasma and lymphoma biopsy was characterized for B\u2010cell proliferation, clonogenicity in soft agar, in vitro tube formation and wound healing. Intracellular signaling was investigated by immunoblotting. HIV p17 protein was detected in reactive lymphoid follicles but not within lymphoma cells. An identical dominant variant p17 sequence, p17\u2010Lyrm, carrying a 117 to 118 Ala\u2010Ala insertion was detected in both plasma and lymphoma tissue. Recombinant p17\u2010Lyrm enhanced B\u2010cell proliferation and clonogenicity promoted the formation of capillary\u2010like structures and enhanced endothelial cell migration. Unlike reference p17, the p17\u2010Lyrm variant enhanced the activation of Akt and ERK, critical kinases in lymphomagenesis. p17\u2010Lyrm clonogenic activity was dependent on the activation of Akt but not of ERK1\/2. These results indicated that HIV p17 variants with distinct molecular signatures and functional properties may accumulate in lymphoid tissues of HIV\u2010infected individuals where they may act as a local stimulus promoting the development of lymphomas.<\/jats:p>","DOI":"10.1002\/hon.2562","type":"journal-article","created":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T21:59:22Z","timestamp":1538085562000},"page":"176-184","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Lymphomagenic properties of a HIV p17 variant derived from a splenic marginal zone lymphoma occurred in a HIV\u2010infected patient"],"prefix":"10.1002","volume":"37","author":[{"given":"Francesca","family":"Caccuri","sequence":"first","affiliation":[{"name":"Section of Microbiology, Department of Molecular and Translational Medicine University of Brescia  Brescia 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