Abstract
AbstractRetinoic acid-inducible gene I(RIG-I) activates mitochondrial antiviral signaling proteins, initiating the antiviral response.RIG-IandRNF135, a ubiquitin ligase regulator, are missing in domestic chickens but conserved in mallard ducks. It was long believed that chickens’RIG-Iloss was linked to increased avian influenza susceptibility. We reinstated both genes in chickens and examined their susceptibility to the avian influenza virus H7N1. UninfectedRIG-I-expressing chickens exhibited shifts in T and B cells, while the H7N1 infection led to severe disease, persistent weight loss, and increased viral replication. Conversely, the co-expression ofRIG-IandRNF135reduced the viral replication and was associated with high inflammatory response. Our data indicate that the loss ofRIG-Iin chickens likely evolved to counteract deleterious inflammation caused by viral infection. We highlight the effects of restoring evolutionary lost genes in birds and suggest a new immunological approach to reduce viral replication and prevent infection.Graphical abstract
Publisher
Cold Spring Harbor Laboratory
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