Host–pathogen co-evolution and glycan interactions

•Coevolution between calicivirus glycan-binding and host glycan diversity is proposed.•Not all individuals in a population are recognized and infected by a given strain.•Evolution of RHDV strain glycan-specificities occurred.•Reciprocal evolution of wild rabbits glycan diversity was documented.•At the population level, host species glycan diversity provides ‘herd innate protection’.

Noroviruses and rotavirus A bind to polymorphic glycans of the histo-blood group type (HBGAs). Norovirus strains that bind to HBGAs can collectively infect all humans but each strain only infects a subgroup of the population, suggesting a past co-evolution that led to a trade-off where the human population is partly protected whilst the virus circulation is maintained. We termed ‘Herd Innate Protection’ the host species partial protection provided by the HBGAs polymorphism. Given its recent emergence, high virulence and HBGAs attachment, RHDV provides a model for studying calicivirus-host co-evolution. Field observations documented evolution of the virus ability to recognize the host HBGAs diversity and reciprocal strain-dependent selection of HBGA phenotypes following outbreaks, indicating host–pathogen co-evolution involving glycan polymorphisms.