Summary
A bioRxiv preprint reports that Chandipura virus infection in neuronal cells involves a shift from weakened antiviral signalling to mitochondrial stress, STING activation and GSDME-linked inflammatory cell death. Experiments targeting STING or GSDME altered neuronal injury, with different effects on viral replication.
A bioRxiv preprint reports that Chandipura virus (CHPV) infection in neuronal cells first weakens antiviral signalling and later engages a mitochondrial stress pathway associated with inflammatory cell death. The researchers link this shift to STING signalling and gasdermin E (GSDME), and report that interfering with either pathway altered neuronal injury.
The findings describe a cell-mechanism study, not a clinical evaluation. They offer a proposed explanation for how CHPV infection may contribute to inflammation and neuronal damage during encephalitis.
From weakened antiviral signalling to mitochondrial stress
Early in infection, the researchers observed reduced levels of MAVS, a signalling adaptor involved in antiviral responses to RNA viruses, alongside weaker type I and III interferon responses. Interferons are signalling proteins that help coordinate antiviral defences.
As infection progressed, the study reports mitochondrial dysfunction, increased mitochondrial reactive oxygen species (mtROS), accumulation of cleaved GSDME at mitochondria and release of mitochondrial DNA into the cell’s cytosol. Cytosolic DNA-sensing pathways can activate STING, an innate-immune signalling protein. In the infected neuronal cells, STING activation coincided with neuroinflammatory signalling and pyroptotic cell death.
Pyroptosis is an inflammatory form of cell death in which gasdermin proteins help disrupt the cell membrane. The researchers’ results connect mitochondrial stress and DNA release with this process, while also suggesting that GSDME and STING influence one another: reducing GSDME lowered STING phosphorylation, and reducing STING lowered GSDME activation.
What pathway-targeting experiments found
Pharmacological inhibition or genetic silencing of STING reduced inflammatory signalling, prevented pyroptotic membrane rupture and protected neurons from cell death. The authors report that these interventions did not significantly affect viral replication. By contrast, depleting GSDME reduced both viral replication and neuronal death.
That difference matters for interpreting the proposed pathway. In these experiments, STING intervention was associated with less inflammatory injury without a significant change in virus replication, while GSDME depletion affected both outcomes. The results point to interacting roles for the two proteins rather than a single, uniform effect on infection.
The work is a preprint based on neuronal-cell experiments. Its findings identify a candidate mechanism for CHPV-associated neuronal injury and make STING a potential target for further study in central nervous system viral infections. Whether the same pathway is important in patients, or could guide treatment, requires evidence beyond these cell experiments.