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A team of researchers at The Hormel Institute, University of Minnesota, led by Associate Professor Vijay Reddy, PhD, published a paper in the leading journal Nature Communications.

The paper, “Structure-derived insights from blood factors binding to the surfaces of different adenoviruses,” reveals new insights on the ways different types of adenoviruses interact with blood coagulation proteins—which is essential for improving vaccine efficacy, gene therapy delivery to cells, and more.

Many viruses evade their host’s immune system by fashioning a disguise for themselves, cloaking themselves in proteins belonging to the host, allowing them to fly under the immune radar undetected. Certain adenoviruses, for example, camouflage themselves using blood coagulation proteins, which assist with blood clotting to stop bleeding after injury.

Adenoviruses (Ads) are often used as viral vectors for vaccine and gene delivery; harmful genes are removed from the virus, and its capsid or shell is used as a “shipping container” to deliver therapeutic genes into a cell. The AstraZeneca and Johnson & Johnson COVID-19 vaccines both make use of adenoviruses.

Using cryoEM technology housed at The Hormel Institute, researchers studied the locations, structural characteristics, and interactions between blood coagulation proteins and different Ads, as well as their possible implications on vector transduction and immune clearance.

The research team learned:

• The conserved structure in various blood clotting factors — gamma-carboxyglutamic acid (GLA) domain — binds in the surface pocket of major capsid protein (hexon) of species-C adenoviruses.

• In addition to interactions mediated by Ca2+ ions, hydrophobic interactions involving a patch of amino acid phenylalanine residues stabilize the binding of these proteins to adenoviruses.

• Subtle differences in the hexon pocket sizes influence the relative affinities of proteins binding to different adenoviruses.

• In addition to the relative binding affinities, inherent flexibility/rigidity of the clotting proteins determine how they shield the surfaces of adenoviruses.

“Differential binding of coagulation factors to adenoviruses may shield these viruses against the immune molecules, thereby affecting their intended cell targets,” Reddy said.

“The insights gained from this work can be used to retarget adenoviruses to tissues and cells of interest,” Reddy added.

Reddy, CryoEM Specialist Janarjan Bhandari, PhD, and Post-Doctoral Associate Olivia Ma, PhD, are all listed as authors of the paper.