Viral gastroenteritis: Models, molecules, and mechanisms

Enteric adenovirus (EAdV) types F40 and F41 constitute a leading cause of diarrhoea and diarrhoea-associated mortality in children.

In 2021-2022, AdV-F41 and adeno-associated virus 2 (AAV-2) were linked to a multi-country outbreak of acute pediatric hepatitis. We lack both vaccines and antiviral drugs for prevention and treatment, respectively, against EAdV-caused disease.

This is largely due to difficulties to isolate these viruses and hence to study infection, resulting in insufficient knowledge about EAdVs and EAdV-caused disease.

Our overall aim is to develop and establish in vitro and ex vivo models of EAdV infection and disease, and to provide novel insights into the molecular mechanisms of cell entry, infection, tropism, and pathogenesis.

We have access to a unique biological toolbox including infectious virus; susceptible cells for efficient EAdV propagation; enteroids that mimic human intestine; authentic body fluids from human stomach, gall bladder, and pancreas; sensory cell lines with characteristics of enterochromaffin cells and tuft cells known to orchestrate nausea, vomiting and diarrhoea; and to hepatoma cells.

We will combine and integrate these tools with expertise and experience of EAdV research, quantitative proteomics, and structural biology to fill important knowledge gaps in the area of viral gastroenteritis.

The programme will point out novel targets for treatments including precision medicine and can be translated to studies of other gut pathogens.