Uncovering the mechanisms behind rotavirus and norovirus disease symptoms

Rotavirus and norovirus infections causes diarrhea and vomiting but also fever and sickness feeling.

While vomiting and sickness symptoms are mediated from the brain, diarrhea is mediated by signals within the enteric nervous system and modulated by CNS efferents.

There is a lack of knowledge how virus infected cells in the intestine signals to neighboring cells, the underlaying enteric glial cells and enteric neurons.

This proposal aims to uncover mechanisms of virus-cell-nerve communication to better understand the signaling that lead to diarrhea, vomiting and sickness feeling.

Using human intestinal enteroids, enteric nerves and glia cells, isolated from human biopsies, a novel intestinal epithelium containing enteric nervous system that mimic the human in vivo situation is build.

With single cell transcriptomics and proteomics, we can identify differences in gene and protein expression from infected as well as neighboring cells.

Using an animal model together with iDISCO, a novel tissue clearing technique and volumetric imaging and computer-aided analysis we will enable high resolution 3D imaging of infection and activation of nerves in the intestine and brain. These studies will provide important information about communication within and between the gut and brain.

Increased knowledge of how the signaling occur and how symptoms appear is important for development of effective treatments.