NARILIS lunch seminar | Prof. Vibhu Prasad, University of Geneva

We are pleased to invite you to a seminar given by

Prof. Vibhu Prasad

Assistant Professor
University of Geneva, Faculty of Medicine, Department of Microbiology and Molecular Medicine

https://www.unige.ch/medecine/mimo/en/groupes/vibhu-prasad

His seminar is entitled:

"Rewiring the stressed cell: lessons from adenovirus infection"

The unfolded protein response is commonly viewed as a cellular defence mechanism triggered by the protein-folding burden of virus infection. Our work suggests a different paradigm: viruses can directly manipulate individual stress sensors to generate signalling states that are distinct from the canonical ER stress response.

Using human adenovirus as a model, we previously identified the viral ER membrane protein E3-19K as a direct activator of the IRE1a–XBP1 pathway. E3-19K interacts with the luminal domain of IRE1a, promotes XBP1 splicing, and establishes a transcriptional programme that feeds back to support viral early gene expression and infection. These findings revealed that adenovirus does not merely tolerate the unfolded protein response, but actively exploits IRE1a signalling.

Our recent work now reveals an additional and mechanistically distinct layer of regulation. The adenoviral early protein E1A interacts with the cytoplasmic domain of IRE1a and promotes dissociation of the inhibitory chaperone BiP, yet this state is not sufficient to induce productive XBP1 splicing. In contrast, E3-19K activates IRE1a–XBP1 signalling while largely preserving BiP association. Thus, two viral proteins acting from opposite sides of the ER membrane uncouple regulatory features that are normally linked during canonical IRE1a activation.

Together, these studies identify adenovirus as a powerful experimental system for dissecting the modular regulation of stress signaling states. More broadly, they suggest that virus–host interactions can reveal previously hidden signalling states of cellular stress sensors and illustrate how pathogens reshape stress-response pathways with remarkable spatial and temporal precision.

Invited by Prof. Nicolas Gillet, UNamur, URVI