Role Of Competition In The Strain Structure Of Rotavirus Under Invasion And Reassortment

Abstract

The role of competitive interactions in the formation and coexistence of viral strains remains unresolved. Neglected aspects of existing strain theory are that viral pathogens are repeatedly introduced from animal sources and readily exchange their genes. The combined effect of introduction and reassortment opposes strain structure, in particular the predicted stable coexistence of antigenically differentiated strains under strong frequency-dependent selection mediated by cross-immunity. Here we use a stochastic model motivated by rotavirus, the most common cause of childhood diarrheal mortality, to investigate serotype structure under these conditions. We describe a regime in which the transient coexistence of distinct strains emerges despite only weak cross-immunity, but is disturbed by invasions of new antigenic segments that reassort into existing backgrounds. We find support for this behavior in global rotavirus sequence data and present evidence for the displacement of new strains towards open antigenic niches. Our work extends previous work to bacterial and viral pathogens that share these rotavirus-like characteristics, with important implications for the effects of interventions such as vaccination on strain composition, and for the understanding of the factors promoting emergence of new subtypes.