Active Infection & Immunity Genetics & Molecular Biology

The role of ZAP in neuronal protection from alphaviruses and transposable elements

Funder Wellcome Charity-funded
Recipient organisation King's College London
Funding Not disclosed
Period Oct 2025 — Sept 2028

In plain English

AI plain-English summary

A protein called ZAP normally helps brain cells destroy viral genetic material, but researchers want to know whether it also keeps the brain’s own rogue DNA in check. When certain viruses—like alphaviruses, which can cause encephalitis—infect neurons, they trigger inflammation that damages brain tissue. Separately, the human genome contains thousands of ancient viral fragments called transposable elements (TEs) that can become active and also spark inflammation. Both processes are linked to neurodegenerative diseases, but it is unclear whether ZAP’s ability to silence TEs protects neurons from this damage, or whether viral infection overwhelms that protection. This project will use human neurons grown from stem cells to map exactly which viral and TE-derived RNAs ZAP binds to, and how that binding affects neuron survival and inflammatory gene activity. If ZAP proves to be a key brake on both viral replication and TE-driven inflammation, it could reveal a single molecular target for therapies that slow neurodegeneration. The work is fundamental science—it will not produce a drug tomorrow—but understanding how a single protein controls two sources of brain inflammation could eventually guide treatments for conditions such as Alzheimer’s or virus-triggered cognitive decline.

View original technical description
Zinc-finger antiviral protein (ZAP) is a cytoplasmic protein restricts viral replication. In addition to restriction of inhibiting viral RNA expression, ZAP has also been shown to target RNA expressed from endogenous transposable elements (TEs) for decay. Viral infection and upregulation of TEs are associated with neurodegenerative conditions. This may be due to sensing of viral RNA or TEs by pattern recognition receptors, which leads to an inflammatory response. This project aims firstly to characterise the restriction of alphavirus infection by ZAP and its cofactors in neurons to understand the components of the ZAP antiviral system that are required in these cells. The second aim of this project is to assess how TE-derived RNA is sensed and targeted for decay in neurons by ZAP and its cofactors in the absence and presence of alphavirus infection and how this affects neuron viability and inflammatory gene expression. These aims will be addressed in iPSC-derived neurons using cross-linking immunoprecipitation (CLIP) to detect direct ZAP or cofactor binding to specific transcripts, transcriptomics to measure transcript abundance, and viral replication assays. The ultimate goal of this project is to understand the mechanism by which ZAP restricts viral RNA and TE-containing RNA in neurons

View the original record at the funder ↗

Researchers

Hannah Jones (EPMC Awardee)

Related Research

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Original classification

PhD Studentship (Basic)

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.