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Volume 105, Issue 4

Molecular mechanisms behind the generation of pro-oncogenic HIV-1 matrix protein p17 variants No Access

Abstract

HIV-1 matrix protein p17 variants (vp17s), characterized by amino acid insertions at the COOH-terminal region of the viral protein, have been recently identified and studied for their biological activity. Different from their wild-type counterpart (refp17), vp17s display a potent B cell growth and clonogenic activity. Recent data have highlighted the higher prevalence of vp17s in people living with HIV-1 (PLWH) with lymphoma compared with those without lymphoma, suggesting that vp17s may play a key role in lymphomagenesis. Molecular mechanisms involved in vp17 development are still unknown. Here we assessed the efficiency of HIV-1 Reverse Transcriptase (RT) in processing this genomic region and highlighted the existence of hot spots of mutation in , at the end of the matrix protein and close to the matrix-capsid junction. This is possibly due to the presence of inverted repeats and palindromic sequences together with a high content of Adenine in the 322–342 nucleotide portion, which constrain HIV-1 RT to pause on the template. To define the recombinogenic properties of hot spots of mutation in the matrix gene, we developed plasmid vectors expressing and a minimally modified variant, and measured homologous recombination following cell co-nucleofection by next-generation sequencing. Data obtained allowed us to show that a wide range of recombination events occur in concomitance with the identified hot spots of mutation and that imperfect events may account for vp17s generation.

  • Received:
  • Accepted:
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Keyword(s): B cell clonogenic activity , evolutionary trajectory , HIV-1 matrix protein p17 variants , hot spots of mutations , next generation sequencing and recombination events
Funding
This study was supported by the:
  • Associazione Italiana per la Ricerca sul Cancro (Award 20108)
    • Principle Award Recipient: ArnaldoCaruso
© 2024 The Authors
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2024-04-30
2024-05-15
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Molecular mechanisms behind the generation of pro-oncogenic HIV-1 matrix protein p17 variants
J. Gen. Virol. 105, 001982 (2024); https://doi.org/10.1099/jgv.0.001982
/content/journal/jgv/10.1099/jgv.0.001982
/content/journal/jgv/10.1099/jgv.0.001982
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