Publication Celebration!

As the days get darker, we are delighted to celebrate two recent publications with strong contributions by our group: a research article and a review. We duly celebrated them with a fika last month.

The research article results from a close collaboration with the groups of Gisa Gerold and Niklas Arnberg, and features a large contribution from Dario.

M. Becker, D.V. Conca, N. Dorma, N. Mistry, E. Hahlin, L. Frängsmyr, M. Bally, N. Arnberg, G. Gerold
Journal of Virology 2023, 97(10), e0077023

It is about entry mechanisms and tropism of enteric adenovirus (EAdV) types F40 and 41, a leading cause of gastroenteritis and diarrhea-associated death in young children. This work highlights the need to study viruses’ infectious behavior and mechanisms in biologically relevant models, particularly cells derived from the organs that they cause disease in: EAdV F40 and 41 displayed significantly faster entry into cells derived from the small intestine (HuTu80), as compared to lung-derived cells traditionally used to study these viruses (A549). Dario contributed an intricate analysis of the movement of fluorescently labeled viral particles on the cell surface, classifying particle motion into four different types. With this, he has shown that the viral particles are also significantly more mobile on HuTu80 cells, i.e., they on average spend more time in free diffusion or directed motion than on A549 cells.

Dario gained further insights by defining a scoring novel parameter for all individual particles’ motion trajectories: the ‘average motion coefficient’ (AMC). In the AMC calculation, freer types of motion get a higher score. This showed that on HuTu80 cells, not all particles are more mobile than on A549 cells, but rather, a considerable population of particles shows heightened mobility after attachment to the plasma membrane. The correlation of faster entry and higher cell surface mobility is an interesting result. It is possibly due to a more efficient scouting of the cell surface for attachment receptors, but that should be investigated further. Overall, it shows how our biophysical and particle tracking expertise can provide unexpected and interesting angles to understanding the behavior of viruses at the cell surface. Well done everyone, and congratulations on the publication!

Single particle tracking experiments. A) Fluorescence microscopy can be used to localize individual fluorescently labelled virus particles with nanometer precision. B) Single particle tracking and live cell microscopy allows us to follow a virus as it lands and diffuses on the cell surface.

More in-depth molecular analysis of interactions of viral particles with the cell surface, yet more zoomed-out across different viruses, can be found in a recent review by Marta and others:

S Olofsson, M. Bally, E. Trybala, T. Bergström
Annurev. Virology 2023, 10, 283

It focuses on the function of viral O-glycans in the life cycle of many viruses. O-glycans are polysugar chains attached to serine or threonine amino acid residues on proteins. They are synthesized by a multitude of cellular enzymes leading to an enormous structural and compositional complexity. This is why their biological role has long remained understudied. Yet, it has recently become more and more evident how important O-glycosylation can be in viral attachment, entry, as well as viral particle release. For example, O-glycans are essential in balancing attractive and repulsive interactions between the virus and the cell surface, so that the viral particle can find its receptor without bouncing off or becoming trapped in the sugar forest covering the cell (glycocalyx). Such intricacies and interactions full of paradoxes are our group’s key interests, which we tackle with the various biophysical tools we have available.

HSV-1 reaching its receptor on the cell surface via balanced repulsive and attractive interactions with the cell’s glycocalyx. Image credit: Yara Abidine