p17 Variant Expression and Evolution in HIV-Mediated Lymphomagenesis

TL;DR

This paper explores how specific p17 protein variants may contribute to lymphoma development in HIV-positive individuals and could help identify those at higher risk.

Contribution

The study identifies specific p17 variants with amino acid insertions that are more prevalent in HIV-positive lymphoma patients and may contribute to cancer development.

Findings

p17 variants with specific amino acid insertions are more common in HIV-positive individuals with lymphoma.

These variants destabilize the protein and interact with PAR-1, potentially driving oncogenesis.

Next-generation sequencing could help screen and monitor high-risk HIV-positive patients for lymphoma.

Abstract

Non-Hodgkin lymphoma (NHL) remains the most common malignancy and cause of death among human immunodeficiency virus (HIV-1)-positive individuals, its prevalence remaining even after the introduction of combined antiretroviral therapy (cART). The mechanisms underlying B-cell tumorigenesis are still poorly understood; however, recently, a key role for p17 variants (vp17s) in lymphoma development has been clearly elucidated. Here, we describe findings on lymphomagenic vp17s and discuss their potential role as diagnostic and prognostic markers that could be used to predict the HIV-positive patients at higher risk of developing lymphoma. Specifically, vp17s endowed with amino acid (aa) insertions in their C-terminal region, at positions 114–115 (Glu-Lys), 117–118 (Ala–Ala) and 125–126 (Gly–Asp), were found to be significantly more prevalent in HIV-positive individuals with lymphoma as compared to those without. Alterations in the primary aa sequences destabilize the protein, exposing a previously hidden functional epitope which interacts with protease-activated receptor-1 (PAR-1) and stimulates the protein kinase B pathway, conferring oncogenic potential to vp17s and possibly contributing to lymphomagenesis. Therefore, ultradeep sequencing technologies, such as next-generation sequencing, could serve as a valuable screening tool for identifying and monitoring the HIV-positive patients at higher risk of developing lymphoma, paving the way for targeted preventive intervention strategies.

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