Enriched pathogen diversity under host-type heterogeneity and immune-mediated competition

Pathogen strains can stably coexist if they specialize on different hosts. Multiple strains can also coexist on a single host through negative frequency-dependent interactions mediated by partial cross-immunity. Understanding pathogen diversity remains a challenge however when both host specificity and cross-immunity are acting and may be functionally linked, as has been proposed for rotavirus, where a single protein is both antigenically important and determines host specificity by binding to the genetically encoded human blood group antigens. This situation is akin to the more general question in ecology of species coexistence when stabilizing and equalizing mechanisms interact. We examine this interaction with a theoretical model motivated by rotavirus and apply an adaptive dynamics framework to show how these two kinds of competition, typically considered separately, affect diversity. When cross-immunity depends on host-pathogen affinity, diversity is magnified as long-term evolution allows for the coexistence of multiple semi-specialized strains, similar to observations in rotavirus. In contrast, the simultaneous co-occurrence of several semi-specialized individuals is not observed when the degree of cross-immunity is independent from affinity distance among strains. The interplay of equalizing and stabilizing mechanisms fundamentally modifies diversity patterns and should be considered when addressing strain coexistence.