Kinetic models for receptor-catalyzed conversion of coxsackievirus B3 to A-particles

The immunoglobulin superfamily protein receptors for poliovirus, human rhinovirus, and coxsackievirus B (CVB) serve to bind the viruses to target cells and to facilitate the release of the virus genome by catalyzing the transition from the mature infectious virus to the A-particle uncoating intermediate. Receptor binding sites characterized by two equilibrium dissociation constants have been identified. The site with higher affinity is best observed at warmer temperatures and appears to correlate with the reversible conformational state in which the capsid is permeable to small molecules and peptides that are buried in the crystal structures are exposed. Measurements of CVB conversion to inactive particles over time in the presence of varied concentrations of soluble coxsackievirus and adenovirus receptor showed that the observed first-order rate constant varies with receptor concentration. The dose-response data, previously modeled as the sum of first-order reactions, have been used to evaluate models for the receptor-catalyzed conversion of CVB that include the high- and low-affinity binding sites associated with capsid breathing. Allosteric models wherein receptor binding shifts the equilibrium toward the open capsid conformation, in which the high-affinity binding site is available, best fit the data.

This paper compares models that relate the structural, mechanistic, and kinetic details of receptor-virus interactions known from previous work with human enteroviruses. New models are derived using recent results from receptor-catalyzed conversion of coxsackievirus B3 to non-infectious A-particles. Of those considered, the acceptable models include the capsid breathing cycle and two conformation-dependent receptor binding sites. The results indicate that the receptor enhancement of virus conversion to A-particles involves allostery through conformation selection.