Coagulation factor IX mediates serotype-specific binding of species A adenoviruses to host cells

Area of Science:

• Virology
• Molecular Biology
• Biochemistry

Background:

• Human adenoviruses (HAdVs) are common pathogens, with species A (HAdV-12, -18, -31) causing severe infections in immunocompromised individuals.
• Adenovirus entry into host cells typically involves interactions with host factors, but mechanisms vary among serotypes.

Purpose of the Study:

• To investigate the role of coagulation factors in the infection mechanisms of human adenovirus species A.
• To compare the binding and infection enhancement of HAdV-18 and HAdV-31 by coagulation factor IX (FIX) versus HAdV-5 by coagulation factor X (FX).

Main Methods:

• Binding and infection experiments using epithelial cells from airways and intestines.
• Surface plasmon resonance to analyze hexon-coagulation factor interactions (affinity, half-life).
• Studies using cells with specific glycosaminoglycans (GAGs) and GAG-cleaving enzymes to assess binding specificity.

Main Results:

• Coagulation factor IX (FIX) significantly enhances binding and infection by HAdV-18 and HAdV-31, but not HAdV-12.
• HAdV-31 hexon-FIX interaction shows higher affinity and different half-life compared to HAdV-5 hexon-FX interaction.
• Both HAdV-31-FIX and HAdV-5-FX complexes bind to cell-surface GAGs, but exhibit distinct GAG dependence and specificity.

Conclusions:

• Coagulation factor IX is a key mediator for HAdV-18 and HAdV-31 cell entry, distinct from the FX pathway used by other adenoviruses.
• The HAdV-31 hexon-FIX interaction presents a potential target for antiviral therapies.
• Findings advance understanding of adenovirus tropism and inform the development of HAdV-based gene/cancer therapy vectors.