Host Genetics: It Is Not Just the Virus, Stupid

Much of the focus of viral pathogenesis is on viral virulence factors; however, virulence can only be defined in the context of a virus–host combination. Furthermore, there is abundant evidence that highly pathogenic viruses have been selected for specific host genetic variants within the target population. The identification and mechanistic dissection of host genetic polymorphisms therefore has powerful implications for our understanding of viral diseases, including the identification of novel therapeutic targets. In this chapter, we review the classical approaches used to identify host allelic variations that regulate disease susceptibility. We also discuss next-generation molecular technologies and computational approaches that are poised to revolutionize our understanding of the impact of host genetic variation on viral diseases at the population level.