Human Full-Length Coagulation Factor X and a GLA Domain-Derived 40-mer Polypeptide Bind to Different Regions of the Adenovirus Serotype 5 Hexon Capsomer

Abstract The interaction of human adenovirus (HAdV)-C5 and many other adenoviruses with blood coagulation factors (e.g., human factor X, FX) involves the binding of their GLA domain to the hexon capsomers, resulting in high levels of hepatotropism and potential hepatotoxicity. In this study, we tested the possibility of preventing these undesirable effects by using a GLA-mimicking peptide as a competitor. An FX GLA domain-derived, 40-mer polypeptide carrying 12 carboxyglutamate residues was synthesized (GLAmim). Surface plasmon resistance (SPR) analysis showed that GLAmim reacted with free and capsid-embedded hexon with a nanomolar affinity. Unexpectedly, GLAmim failed to compete with FX for hexon binding, and instead significantly increased the formation of FX–hexon or FX–adenovirion complexes. This observation was confirmed by in vitro cell transduction experiments using HAdV-C5-Luciferase vector (HAdV5-Luc), as preincubation of HAdV5-Luc with GLAmim before FX addition resulted in a higher transgene exp...