Pathological Mechanisms Involved in HIV-Associated Lymphomagenesis: Novel Targeted Therapeutic Approaches

The intricate interplay of direct and indirect mechanisms relating to immune dysfunction, chronic inflammation, and viral proteins represents a key factor of lymphomagenesis in HIV-infected patients. Indirect mechanisms based on cytokine dysregulation, HIV-induced immune dysfunction, and co-infectio...

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Main Authors: Mihaela Straista, Francesca Caccuri, Nicoleta Arnaut, Arnaldo Caruso, Mark Slevin
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/10/705
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author Mihaela Straista
Francesca Caccuri
Nicoleta Arnaut
Arnaldo Caruso
Mark Slevin
author_facet Mihaela Straista
Francesca Caccuri
Nicoleta Arnaut
Arnaldo Caruso
Mark Slevin
author_sort Mihaela Straista
collection DOAJ
description The intricate interplay of direct and indirect mechanisms relating to immune dysfunction, chronic inflammation, and viral proteins represents a key factor of lymphomagenesis in HIV-infected patients. Indirect mechanisms based on cytokine dysregulation, HIV-induced immune dysfunction, and co-infections with oncogenic viruses induce chronic B-cell activation and generation of a prone environment for malignant transformation and tumor growth. Direct mechanisms arise from oncogenic influences of p17, Tat, and Nef HIV proteins, which generate genomic instability, alteration of cellular signaling, and activation of oncogenic pathways. Vp17’s implication in lymphomagenesis and angiogenesis, ensured by activation of PAR1/EGFR/PI3K/Akt and MEK/ERK1/2 pathways, emphasizes the critical need for developing therapeutic strategies that target their signaling mechanisms. This review shows an insight into the pathological mechanisms involved in lymphomagenesis in HIV-infected individuals, focusing on finding novel therapeutic approaches directed at immune rehabilitation and oncogenic signaling pathways.
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spelling doaj-art-de131be89d134651bf3561e2232c455c2025-08-20T01:56:16ZengMDPI AGCells2073-44092025-05-01141070510.3390/cells14100705Pathological Mechanisms Involved in HIV-Associated Lymphomagenesis: Novel Targeted Therapeutic ApproachesMihaela Straista0Francesca Caccuri1Nicoleta Arnaut2Arnaldo Caruso3Mark Slevin4Centre for Advanced Medical and Pharmaceutical Research, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, 540142 Targu Mures, RomaniaCentre for Advanced Medical and Pharmaceutical Research, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, 540142 Targu Mures, RomaniaCentre for Advanced Medical and Pharmaceutical Research, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, 540142 Targu Mures, RomaniaCentre for Advanced Medical and Pharmaceutical Research, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, 540142 Targu Mures, RomaniaCentre for Advanced Medical and Pharmaceutical Research, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, 540142 Targu Mures, RomaniaThe intricate interplay of direct and indirect mechanisms relating to immune dysfunction, chronic inflammation, and viral proteins represents a key factor of lymphomagenesis in HIV-infected patients. Indirect mechanisms based on cytokine dysregulation, HIV-induced immune dysfunction, and co-infections with oncogenic viruses induce chronic B-cell activation and generation of a prone environment for malignant transformation and tumor growth. Direct mechanisms arise from oncogenic influences of p17, Tat, and Nef HIV proteins, which generate genomic instability, alteration of cellular signaling, and activation of oncogenic pathways. Vp17’s implication in lymphomagenesis and angiogenesis, ensured by activation of PAR1/EGFR/PI3K/Akt and MEK/ERK1/2 pathways, emphasizes the critical need for developing therapeutic strategies that target their signaling mechanisms. This review shows an insight into the pathological mechanisms involved in lymphomagenesis in HIV-infected individuals, focusing on finding novel therapeutic approaches directed at immune rehabilitation and oncogenic signaling pathways.https://www.mdpi.com/2073-4409/14/10/705HIVlymphomagenesisvp17therapeutic approacheschronic B cell activation
spellingShingle Mihaela Straista
Francesca Caccuri
Nicoleta Arnaut
Arnaldo Caruso
Mark Slevin
Pathological Mechanisms Involved in HIV-Associated Lymphomagenesis: Novel Targeted Therapeutic Approaches
Cells
HIV
lymphomagenesis
vp17
therapeutic approaches
chronic B cell activation
title Pathological Mechanisms Involved in HIV-Associated Lymphomagenesis: Novel Targeted Therapeutic Approaches
title_full Pathological Mechanisms Involved in HIV-Associated Lymphomagenesis: Novel Targeted Therapeutic Approaches
title_fullStr Pathological Mechanisms Involved in HIV-Associated Lymphomagenesis: Novel Targeted Therapeutic Approaches
title_full_unstemmed Pathological Mechanisms Involved in HIV-Associated Lymphomagenesis: Novel Targeted Therapeutic Approaches
title_short Pathological Mechanisms Involved in HIV-Associated Lymphomagenesis: Novel Targeted Therapeutic Approaches
title_sort pathological mechanisms involved in hiv associated lymphomagenesis novel targeted therapeutic approaches
topic HIV
lymphomagenesis
vp17
therapeutic approaches
chronic B cell activation
url https://www.mdpi.com/2073-4409/14/10/705
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AT francescacaccuri pathologicalmechanismsinvolvedinhivassociatedlymphomagenesisnoveltargetedtherapeuticapproaches
AT nicoletaarnaut pathologicalmechanismsinvolvedinhivassociatedlymphomagenesisnoveltargetedtherapeuticapproaches
AT arnaldocaruso pathologicalmechanismsinvolvedinhivassociatedlymphomagenesisnoveltargetedtherapeuticapproaches
AT markslevin pathologicalmechanismsinvolvedinhivassociatedlymphomagenesisnoveltargetedtherapeuticapproaches