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Updated: May 10, 2025
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A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
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p17 Variant Expression and Evolution in HIV-Mediated Lymphomagenesis.
Nicoleta Arnaut1, Mark Slevin1, Claudia Bănescu1,2
1Centre for Advanced Medical and Pharmaceutical Research, "George Emil Palade" University of Medicine, Pharmacy, Science and Technology, 540142 Targu Mures, Romania.
Viruses
|April 26, 2025
Summary
Specific p17 variants (vp17s) with C-terminal amino acid insertions are more common in individuals with HIV-1 and lymphoma. These vp17s may serve as biomarkers for lymphoma risk in HIV-positive patients.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Non-Hodgkin lymphoma (NHL) is a leading cause of death in individuals with human immunodeficiency virus (HIV-1), persisting despite combined antiretroviral therapy (cART).
- The precise mechanisms driving B-cell tumorigenesis in HIV-1-positive individuals are not fully understood.
- Recent research highlights a significant role for p17 variants (vp17s) in the development of lymphoma.
Purpose of the Study:
- To elucidate the role of specific p17 variants (vp17s) in lymphomagenesis among HIV-1-positive individuals.
- To evaluate the potential of vp17s as diagnostic and prognostic markers for identifying patients at high risk of lymphoma.
- To explore the molecular mechanisms by which vp17s contribute to lymphoma development.
Main Methods:
- Comparative analysis of vp17 sequences in HIV-1-positive individuals with and without lymphoma.
- Utilizing ultradeep sequencing technologies, such as next-generation sequencing, for comprehensive vp17 analysis.
- Investigating the interaction of altered vp17s with protease-activated receptor-1 (PAR-1) and downstream signaling pathways like protein kinase B.
Main Results:
- vp17s with specific C-terminal amino acid insertions (at positions 114-115, 117-118, and 125-126) were significantly more prevalent in HIV-1-positive patients with lymphoma compared to those without.
- These alterations destabilize the vp17 protein, exposing a functional epitope that interacts with PAR-1.
- This interaction stimulates the protein kinase B pathway, suggesting an oncogenic role for these vp17 variants.
Conclusions:
- Specific vp17 variants with C-terminal amino acid insertions are strongly associated with lymphoma development in HIV-1-positive individuals.
- These lymphomagenic vp17s represent potential biomarkers for early detection and risk stratification of lymphoma in this population.
- Next-generation sequencing can be a valuable tool for screening and monitoring HIV-1-positive patients, enabling targeted preventive strategies against lymphoma.
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