Antigenic Shielding with a Dynamically Evolving Cross-Reactivity Network

Long-term viral persistence within hosts in commonly explained by immune escape, where the rapid mutations enable evasion from immune elimination. Another mechanism, antigenic shielding, emerges from cooperative interactions among viral variants through immune cross-reactivity. In this study we develop a stochastic coevolution model that integrates viral mutation dynamics with a dynamically evolving cross-reactivity network (CRN). The probability of forming a cross-reactivity link depends on the phylogenetic distance between variants. Our simulation shows that antigenic shielding can substantially extend the lifetime of moderately mutating viruses that would otherwise be quickly eliminated by immune system. The simulated averages of variant progeny number and virus population extinction time are consistent with analytical predictions from stochastic process theory. This framework offers a quantitative perspective on intra-host virus–immune coevolution and provides insights into persistent infections such as HCV.