Integration events in the Life Cycle of HIV-2, and its susceptibility to Lenacapavir and Integrase Strand Transfer Inhibitors

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dc.contributor.advisorMohamed, Mahdi
dc.contributor.authorKiarie, Irene
dc.contributor.departmentMolekuláris sejt- és immunbiológia doktori iskolahu
dc.contributor.submitterdepÁltalános Orvostudományi Kar
dc.date.accessioned2026-02-09T12:00:35Z
dc.date.available2026-02-09T12:00:35Z
dc.date.defended2026-02-23
dc.date.issued2026
dc.description.abstractHuman immunodeficiency virus type 2 (HIV-2) is less pathogenic and less extensively studied than HIV-1, despite its clinical relevance in West Africa and in countries with socio-colonial ties with West Africa. This dissertation investigates key aspects of HIV-2 biology, focusing on viral integration, susceptibility to antiretroviral agents, and the role of the accessory protein Vpx in host-virus interactions. The antiviral activity of all currently approved integrase strand transfer inhibitors and the capsid inhibitor lenacapavir was evaluated against HIV-2 using cell-based assays and supported by in silico molecular docking analyses. In parallel, transcriptomic and functional approaches were used to examine the effects of HIV-2 Vpx on host gene expression, cytokine secretion, and HIV-1 Tat expression in THP-1 monocytic cells. Furthermore, a comparative genome wide integration site analysis was performed to identify differences between HIV-1 and HIV-2 integration patterns in Jurkat cells. The results demonstrate that HIV-2 is susceptible to integrase strand transfer inhibitors and lenacapavir. Vpx induces broad changes in host transcriptional and inflammatory pathways, and that HIV-2 displays distinct chromatin and chromosomal integration preferences compared with HIV-1. These findings advance understanding of HIV-2 biology and support the use of current and emerging antiretroviral agents for HIV-2 infection.
dc.format.extent116
dc.identifier.urihttps://hdl.handle.net/2437/404113
dc.language.isoen
dc.subjectHIV-2, integration, Integrase Strand Transfer Inhibitors(INSTIs), lenacapavir,Vpx, integrase, LEDGF/p75
dc.subject.disciplineElméleti orvostudományokhu
dc.subject.sciencefieldOrvostudományokhu
dc.titleIntegration events in the Life Cycle of HIV-2, and its susceptibility to Lenacapavir and Integrase Strand Transfer Inhibitors
dc.title.translatedIntegrációs események a HIV-2 életciklusában, valamint érzékenysége a Lenacapavirra és az Integráz Strand Transfer inhibitorokra
dc.typePhD, doktori értekezéshu
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