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Diarrhoea-Associated Human Adenovirus Structure Mapped for the First Time

HUMAN adenovirus (HAdV) types F40 and F41 are prominent causes of diarrhoea and diarrhoea-associated mortality in more than 50,000 young children worldwide annually. For the first time, researchers have successfully mapped the structure of an enteric HAdV-F41 that may in the long term aid in the treatment for other viral diseases, including coronavirus disease (COVID-19).

Adenoviruses are frequent pathogens in humans which can lead to infections in the airways, eyes, intestines, liver, and urinary tract. In addition to causing diseases in humans, several HAdV have been investigated as vaccine vehicles against infectious diseases, such as COVID-19, Middle East respiratory syndrome (MERS), Ebola disease, AIDS, and Zika virus disease.

To infect the intestines, the enteric adenoviruses that cause gastrointestinal diseases need to be equipped to pass through the acidic environment of the stomach without being broken down. Using the advanced cryo-electron microscope available at Umeå University, Umeå, Sweden, the researchers were able to take detailed images of HAdV-F41 to map a three-dimensional puzzle exhibiting what the virus looks like down to the atomic level. The virus is one of the most complex structures studied at this level, with the shell, which protects the virus’ genome, consisting of 2,000 protein molecules with a total of 6 million atoms. The research revealed that the HAdV-F41 structure remained unchanged even at the low pH of the stomach. Further findings included understanding differences compared to respiratory adenoviruses in how a particular protein is modified in the shell of the virus, as well as new insights into how the virus packs its genome inside the shell.

Together, the study provided an increased understanding of the pathogenicity of the virus. Assistant Prof Lars-Anders Carlson noted: “Continued research can provide answers to whether this property can also be used to create vaccines that ride ‘free rides’ and thus be given in edible form instead of as syringes.” The teams hope that, in the long run, the virus’ abilities could be used as a tool to fight disease, perhaps even COVID-19.