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Research Project: Intervention Strategies to Prevent and Control Disease Outbreaks Caused by Emerging Strains of Avian Influenza Viruses

Location: Exotic & Emerging Avian Viral Diseases Research

Title: Mutations in PB1, NP, HA, and NA contribute to increased virus fitness of H5N2 highly pathogenic avian influenza virus clade 2.3.4.4 in chickens

Author
item YOUK, SONGSU - Orise Fellow
item LEYSON, CHRISTINA - Orise Fellow
item SEIBERT, BRITTANY - University Of Georgia
item PEREZ, DANIEL - University Of Georgia
item JADHAO, SAMADHAN - Emory University, School Of Medicine
item Suarez, David
item Pantin Jackwood, Mary

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/18/2020
Publication Date: 2/10/2021
Citation: Youk, S., Leyson, C., Seibert, B., Perez, D., Jadhao, S., Suarez, D.L., Pantin Jackwood, M.J. 2021. Mutations in PB1, NP, HA, and NA contribute to increased virus fitness of H5N2 highly pathogenic avian influenza virus clade 2.3.4.4 in chickens. Journal of Virology. 95(5):e01675-20. https://doi.org/10.1128/JVI.01675-20.
DOI: https://doi.org/10.1128/JVI.01675-20

Interpretive Summary: Highly pathogenic avian influenza (HPAI) viruses of the A/goose/Guangdong/1/96 subtype H5Nx lineage continue to circulate worldwide affecting both poultry and wild birds. The H5N8 HPAI clade 2.3.4.4 virus, after mixing with wild bird AI viruses, generated the H5N2 HPAI virus that caused the severe outbreak in poultry in the United States in 2015. Viruses isolated later during the outbreak were more infectious and transmissible in chickens than the initial wild bird H5N2 virus. This study determined which of the mutations that occurred as the H5N2 virus circulated in poultry are associated with this increase in virus fitness in chickens. We found that mutations in the PB1, NP, HA, and NA virus proteins contributed to the adaptation of the H5N2 HPAI virus in chickens. This knowledge is important for understanding the epidemiology of AI viruses and the changes related to adaptation of wild bird AI virus in poultry species.

Technical Abstract: The H5N8 highly pathogenic avian influenza (HPAI) clade 2.3.4.4 virus spread to North America by wild birds and reassorted to generate the H5N2 HPAI virus that caused the severe outbreak in poultry in the United States in 2015. In previous studies we showed that H5N2 viruses isolated from poultry in the later stages of the outbreak had higher infectivity and transmissibility in chickens than the wild bird index H5N2 virus. In this study we determined the genetic changes that contributed to the difference in host virus fitness by analyzing sequence data from all the viruses detected during the H5N2 outbreak, and by studying the pathogenicity of reassortant viruses generated with the index wild bird virus and a chicken virus from later in the outbreak. Viruses with the index wild bird virus backbone and either PB1, NP, or the entire polymerase complex of the chicken isolate, caused higher and earlier mortality in chickens, with three mutations (PB1 E180D/M317V and NP I109T) identified to contribute to increased polymerase activity in chicken cells. The reassortant virus with the HA and NA from the chicken virus, which mutations were acquired as the virus circulated in turkeys and later in chickens (HA L7P/M66I/S141P/L322Q, NA R253K/S416G), showed faster virus growth and bigger plaque size and enhanced heat persistence in vitro, and increased transmissibility in chickens. Collectively, these findings demonstrate an evolutionary pathway in which an HPAI virus from wild birds can accumulate genetic changes to increase fitness in domestic chickens.