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

Kelsey Briggs; Klaudia Chrzastek; Karen Segovia; Jongsuk Mo; Darrell R Kapczynski

doi:10.1016/j.virol.2024.110066

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

Virology. 2024 Mar 31:595:110066. doi: 10.1016/j.virol.2024.110066. Online ahead of print.

Authors

Kelsey Briggs¹, Klaudia Chrzastek¹, Karen Segovia¹, Jongsuk Mo¹, Darrell R Kapczynski²

Affiliations

¹ Exotic and Emerging Avian Diseases Research Unit, Southeast Poultry Research Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, USDA, 934 College Station Road, Athens, GA, 30605, Georgia.
² Exotic and Emerging Avian Diseases Research Unit, Southeast Poultry Research Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, USDA, 934 College Station Road, Athens, GA, 30605, Georgia. Electronic address: darrell.kapczynski@usda.gov.

PMID: 38574415
DOI: 10.1016/j.virol.2024.110066

Abstract

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.

Keywords: Avian influenza; Chickens; Gene-editing; Mouse Mx1; Replication; Transgene.