The Collaborative Cross as a Model for Studying Viral Infections

Inbred mouse strains are an invaluable resource for modeling virus-host interactions and studying how specific host genes affect virus-induced disease. However, many viruses cause a spectrum of disease outcomes in humans ranging from asymptomatic infection to severe disease or death. Conventional mouse strains do not recapitulate human genetic diversity and often fail to reproduce the full spectrum of virus-induced disease phenotypes seen in humans. The Collaborative Cross (CC) recombinant inbred mouse population is a genetically diverse set of mouse strains designed to model the genetic and phenotypic diversity seen in human populations. The CC has been used to study the effect of host genetic variation on the pathogenesis of several human viruses, and we review the utility of the CC as a resource both for developing new models of virus-induced disease and for the identification and study of host gene variants that affect susceptibility to virus-induced disease.