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In addition to the immune deficiency caused by AIDS and other cofactors, it has been shown that circulating HIV\u20101 proteins play a critical role in lymphoma development. The HIV\u20101 matrix protein p17 (refp17) is released from infected cells and accumulates in lymph nodes of PLWHIV, even during effective pharmacological control of viral replication. Circulating refp17 deregulates the biological activity of different immune cells. Moreover, p17 variants (vp17s) characterized by peculiar amino acid insertions occurring in the C\u2010terminal region of the protein, differently from the refp17, also induce B\u2010cell growth and clonogenicity. Notably, vp17s were found at a significantly higher prevalence in PLWHIV with than without lymphoma. HIV\u20101 mutants expressing clonogenic vp17s are actively spreading, and their prevalence is globally increasing worldwide. RNA viruses exist as a population of quasi\u2010species, transmitted from one host to another, which ultimately leads to viral evolution by generating new master sequences. Here, we developed a next\u2010generation sequence approach to evaluate the frequency of vp17 quasi\u2010species in PLWHIV upon time and demonstrated that the incidence of vp17s also increases at quasi\u2010species levels. Additionally, we established a regression model capable of predicting the insertions with higher probability to be fixed, further highlighting the evolutionary relevance of the C\u2010terminal region in the adaptation of p17 to the human host.<\/jats:p>","DOI":"10.1002\/mbo3.70280","type":"journal-article","created":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T02:17:32Z","timestamp":1775269052000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Decoding HIV\u20101 Next Move Through Matrix Protein p17 Quasi\u2010Species"],"prefix":"10.1002","volume":"15","author":[{"given":"Serena","family":"Messali","sequence":"first","affiliation":[{"name":"Section of Microbiology, Department of Molecular and Translational Medicine University of Brescia Brescia Italy"},{"name":"Division of Microbiology ASST\u2010Spedali Civili Brescia 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