Thursday, August 22, 2024

CEEZAD researchers explore potential for gene editing of pigs to control influenza A virus

An article co-authored by the Director of the Center of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD, www.ceezad.org) and the Center on Emerging and Zoonotic Infectious Diseases (CEZID; https://www.k-state.edu/cezid/) explores the potential for commercial use of gene edited pigs to minimize economic losses caused by Influenza A virus.

The article was co-authored by Dr. Juergen A. Richt, Regents and University Distinguished Professor at Kansas State University and director of CEEZAD and CEZID. Other co-authors include Taeyong Kwon, Bianca L. Artiaga, Chester McDowell, Jamie Retallick, Natasha Gaudreault and Igor Morozov, all from KSU, and collaborators from U. Missouri and Genus plc..

Proteolytic activation of the hemagglutinin (HA) glycoprotein by host cellular proteases is pivotal for influenza A virus (IAV) infectivity. Highly pathogenic avian influenza viruses possess the multibasic cleavage site of the HA, which is cleaved by ubiquitous proteases, such as furin. In contrast, the monobasic HA motif is recognized and activated by trypsin-like proteases, such as the transmembrane serine protease 2 (TMPRSS2).

In this study, CEEZAD researchers aimed to determine the effects of TMPRSS2 on the replication of pandemic H1N1 and H3N2 subtype IAVs in the natural host, the pig. The use of the CRISPR/Cas 9 system led to the establishment of homozygous gene edited (GE) TMPRSS2 knockout (KO) pigs. Delayed IAV replication was demonstrated in primary respiratory cells of KO pigs in vitro. IAV infection in vivo resulted in significant reduction of virus shedding in the upper respiratory tract, and lower virus titers and pathological lesions in the lower respiratory tract of TMPRSS2 KO pigs as compared to WT pigs.

The study’s findings could support the commercial use of GE pigs to minimize (i) the economic losses caused by IAV infection in pigs, and (ii) the emergence of novel IAVs with pandemic potential through genetic reassortment in the "mixing vessel", the pig.

The full article can be read by following this link: Gene editing of pigs to control influenza A virus infections: https://www.tandfonline.com/doi/full/10.1080/22221751.2024.2387449