Active Infection & Immunity

Neuro-Immune Interactions in Heath and Disease - Investigating the Neuropathogenesis of Alphavirus Infections

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

Mosquito-borne alphaviruses are invading the brain of infected fetuses, disrupting the development of neural circuits before birth. This matters because climate change is expanding the range of the mosquitoes that carry these viruses, yet scientists do not understand how the virus crosses from the mother into the fetal brain, or what damage it does once there. In adults, alphavirus infections can cause long-term neurological problems; in children infected before birth, they are linked to developmental delays. The fundamental mechanisms remain unknown. This project uses Sindbis virus—a well-studied model alphavirus—to map exactly how the virus enters the developing brain and what it does to neural progenitor cells, the cells that build the cortex. The researchers will combine human organoids, fetal brain tissue, and zebrafish embryos to track infection and immune responses. If successful, this work will identify the molecular pathways that allow alphaviruses to invade the fetal brain and whether the body’s own immune response helps or harms. That knowledge is purely fundamental science for now, but it lays the groundwork for future therapies that could block neuroinvasion or protect developing neurons—a step toward preventing a class of birth defects that may become more common as mosquito habitats shift.

View original technical description
Neurotropic alphaviruses cause severe disease in humans, and present a growing public health risk following climate change-driven increases in the ecological niche of their mosquito vectors. Alphavirus invasion of the central nervous system (CNS) can result in long-term neurological issues in adults, with observations of neurodevelopmental delays in perinatally infected children. Despite growing infection risks the mechanisms of alphavirus neuroinvasion, its neuropathological consequences, and resulting host immune responses are not well characterised. This is particularly relevant in foetal infections following vertical transmission in utero, where the impact of neuroinvasion on cortical development, progenitor dynamics, and cell fate decisions remain poorly understood. Using Sindbis virus (SINV), a prototypical alphavirus, this project aims to (i) elucidate the key cellular and molecular mechanisms underpinning alphavirus neuroinvasion and neuropathophysiology in developing brain, and (ii) provide insights into host immune responses to alphavirus infection and whether these are protective or pathologic. This work will achieve these aims by leveraging complementary in vitro and in vivo models (human ChP organoids, foetal brain tissue slices, immune cultures, zebrafish embryos), laying essential groundwork for the identification of potential molecular targets for future therapeutic interventions. Key Words: Sindbis virus, Choroid plexus, Cortical development, Neuroimmunology

View the original record at the funder ↗

Researchers

Michael Ellis (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Hijacking the host: molecular strategies of neurotropic enteric viruses
Bunyavirus Immunity Consortium: Delineating the immune response against CCHFV and other Nairoviruses to aid effective vaccine design
Mosquito-borne viruses; targeting the bite.
Understanding Zika virus-induced neuropathogenesis and neurotropism
Microglia and type I interferon: protective and pathogenic mechanisms

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.