Host genes and influenza pathogenesis in humans: an emerging paradigm

• Host genes play an important role in the pathogenesis of influenza virus infection.
• High-throughput technologies accelerate the discovery of susceptibility genes.
• Host susceptibility studies facilitate the development of host-targeted therapy.
• Host-targeted therapy may allow individualized treatment for influenza.

The emergence of the pandemic influenza virus A(H1N1)pdm09 in 2009 and avian influenza virus A(H7N9) in 2013 provided unique opportunities for assessing genetic predispositions to severe disease because many patients did not have any underlying risk factor or neutralizing antibody against these agents, in contrast to seasonal influenza viruses. High-throughput screening platforms and large human or animal databases from international collaborations allow rapid selection of potential candidate genes for confirmatory functional studies. In the last 2 years, at least seven new human susceptibility genes have been identified in genetic association studies. Integration of knowledge from genetic and phenotypic studies is essential to identify important gene targets for treatment and prevention of influenza virus infection.