The following is a summary of “DDX58 Is Associated With Susceptibility to Severe Influenza Virus Infection in Children and Adolescents,” published in the December 2022 issue of Infectious Disease by Lee, et al.

An infection with the seasonal influenza virus can result in a variety of illness severity, including lower respiratory tract infection with respiratory failure. For a study, researchers sought to determine the relationship between frequent variations in the genes that control interferon (IFN) and a child’s vulnerability to a serious influenza illness.

With 348 children from 24 US hospitals hospitalized in the intensive care unit with influenza infection but without risk factors for severe influenza infection (PICFlu cohort, 59.4% male), they performed targeted sequencing of 69 influenza-associated candidate genes. 675 asthmatic kids from the CAMP cohort (62.5% boys) had their complete genomes sequenced to serve as controls. They generated the IFN gene signature score and evaluated the gene’s functional importance using the gene’s levels of expression in PICFlu whole blood.

The retinoic acid-inducible gene I (RIG-I) receptor is encoded by the common variation DDX58, and this variant showed an association above or close to the Bonferroni-corrected threshold. It was shown that the intronic single-nucleotide polymorphism rs4487862 minor allele was related to lower DDX58 expression and IFN signature (P< .05 and P =.0009, respectively), suggesting the effect of the genetic variations on RIG-I and IFN immunity.

They provided data linking frequent gene variations in DDX58 to children’s vulnerability to severe influenza illness. In order to stop a potentially fatal influenza-related illness, RIG-I may be necessary.