Genetic insertion of mouse Myxovirus-resistance gene 1 increases innate resistance against both high and low pathogenic avian influenza virus by significantly decreasing replication in chicken DF1 cell line

Avian influenza virus (AIV) is a constant threat to animal health with recent global outbreaks resulting in the death of hundreds of millions of birds with spillover into mammals. Myxovirus-resistance (Mx) proteins are key mediators of the antiviral response that block virus replication. Mouse (Mu) Mx (Mx1) is a strong antiviral protein that interacts with the viral nucleoprotein to inhibit polymerase function. The ability of avian Mx1 to inhibit AIV is unclear. In these studies, Mu Mx1 was stably introduced into chicken DF1 cells to enhance the immune response against AIV. Following infection, titers of AIV were significantly decreased in cells expressing Mu Mx1. In addition, considerably less cytopathic effect (CPE) and matrix protein staining was observed in gene-edited cells expressing Mu Mx1, suggesting Mu Mx1 is broadly effective against multiple AIV subtypes. This work provides foundational studies for use of gene-editing to enhance innate disease resistance against AIV. •Here we demonstrate stable insertion of the mouse Myxovirus-resistance gene-1 (Mx1) in avian DF1 cells.•Mouse Mx1 enhances innate immune resistance to avian influenza virus (AIV), whereas avian Mx1 appears to be ineffective against AIV.•Transgenic insertion of mouse Mx1 into avian DF1 cells reduced replication of both high and low pathogenic AIV.•These studies demonstrate a potential mechanism to enhance disease resistance to AIV in birds.