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Defining the Landscape of Transcriptional Activity during HIV-1 Infection

Project description

Mapping HIV transcriptional activity

HIV remains a major global health challenge affecting approximately 38 million people worldwide. While antiretroviral therapy controls the virus effectively, it cannot eliminate silent viral reservoirs that persist in immune cells and regenerate infection if treatment stops. Understanding what determines whether these dormant viruses remain silent or become reactivated is critical for developing a cure. With the support of the Marie Skłodowska-Curie Actions programme, the DELTA-HIV project applies cutting-edge transcriptomic approaches to map HIV transcriptional activity at unprecedented resolution. By characterising viral and host gene expression dynamics in primary immune cell models and samples from people living with HIV, the project aims to identify predictive markers of viral reactivation and inform next-generation HIV cure strategies.

Objective

DELTA-HIV (Defining the Landscape of Transcriptional Activity during HIV-1 Infection) addresses a central barrier to curing HIV: the persistence of transcriptionally silent but reactivatable proviruses in latently infected CD4⁺ T cells. Current cure strategies have limited efficacy, in part because transcriptional competence is poorly defined and standard assays rely on indirect, steady-state RNA measurements that miss early or abortive activity. This Fellowship will apply nascent transcriptomic approaches, specifically PRO-Seq, to resolve HIV-1 transcriptional dynamics at nucleotide resolution. Three interlinked work packages will: (1) map host and viral nascent transcription during infection and define how accessory proteins (Vpu/Vpr) rewire RNA polymerase II activity; (2) quantify Pol II dynamics at integrated proviruses in primary CD4⁺ latency models to identify predictive markers of reactivation; and (3) benchmark the rebound potential of latent reservoirs in people living with HIV (PLWH) using paired nascent and mRNA-Seq with integration-normalised analysis. DELTA-HIV directly addresses key knowledge gaps, seeking to refine biomarker discovery, inform therapeutic targeting, and advance global HIV cure strategies in line with Horizon Europe’s goals to reduce the burden of infectious disease.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

KING'S COLLEGE LONDON
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 260 347,92
Address
STRAND
WC2R 2LS London
United Kingdom

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Region
London Inner London — West Westminster
Activity type
Higher or Secondary Education Establishments
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Total cost

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