TY - JOUR
T1 - The molecular basis of differential host responses to avian influenza viruses in avian species with differing susceptibility
AU - Morris, Katrina
AU - Mishra, Anamika
AU - Raut, Ashwin Ashok
AU - Gaunt, Eleanor
AU - Borowska, Dominika
AU - Kuo, Richard
AU - Wang, Bo
AU - Vijayakumar, Periyasamy
AU - Chingtham, Santhalembi
AU - Dutta, Rupam
AU - Baillie, J Kenneth
AU - Digard, Paul
AU - Vervelde, Lonneke
AU - Burt, Dave
AU - Smith, Jacqueline
N1 - Funding Information:
This work was supported by the Biotechnology and Biological Sciences Research Council (grant number BB/L004666/1) and Department of Biotechnology, Government of India (grant number BT/IN/Indo-UK/FADH/48/AM/2013). KM was partly supported by a National Health and Medical Research Council Overseas Postdoctoral Fellowship. The University of Edinburgh provided funding for open access publication fees. LV received funding from the European Union’s Horizon 2020 (VetBioNet) research and innovation program under grant agreement N° 731014. Additional funding was provided by BBSRC strategic program grant funding (BBS/E/D/20002173 and BBS/E/D/20002174) to LV.
Funding Information:
This work was supported by the Biotechnology and Biological Sciences Research Council (grant number BB/L004666/1) and Department of Biotechnology, Government of India (grant number BT/IN/Indo-UK/FADH/48/AM/2013). KM was partly supported by a National Health and Medical Research Council Overseas Postdoctoral Fellowship. The University of Edinburgh provided funding for open access publication fees. LV received funding from the European Union’s Horizon 2020 (VetBioNet) research and innovation program under grant agreement N° 731014. Additional funding was provided by BBSRC strategic program grant funding (BBS/E/D/20002173 and BBS/E/D/20002174) to LV. Acknowledgments
Publisher Copyright:
Copyright © 2023 Morris, Mishra, Raut, Gaunt, Borowska, Kuo, Wang, Vijayakumar, Chingtham, Dutta, Baillie, Digard, Vervelde, Burt and Smith.
PY - 2023/2/28
Y1 - 2023/2/28
N2 - Highly pathogenic avian influenza (HPAI) viruses, such as H5N1, continue to pose a serious threat to animal agriculture, wildlife and to public health. Controlling and mitigating this disease in domestic birds requires a better understanding of what makes some species highly susceptible (such as turkey and chicken) while others are highly resistant (such as pigeon and goose). Susceptibility to H5N1varies both with species and strain; for example, species that are tolerant of most H5N1 strains, such as crows and ducks, have shown high mortality to emerging strains in recent years. Therefore, in this study we aimed to examine and compare the response of these six species, to low pathogenic avian influenza (H9N2) and two strains of H5N1 with differing virulence (clade 2.2 and clade 2.3.2.1) todetermine how susceptible and tolerant species respond to HPAI challenge. Birds were challenged in infection trials and samples (brain, ileum and lung) were collected at three time points post infection. The transcriptomic response of birds was examined using a comparative approach, revealing several important discoveries. We found that susceptible birds had high viral loads and strong neuro inflammatory response in the brain, which may explain the neurological symptoms and high mortality rates exhibited following H5N1 infection. We discovered differential regulation of genes associated with nerve function in the lung and ileum, with stronger differential regulation in resistant species. This has intriguing implications for the transmission of the virus to the central nervoussystem (CNS) and may also indicate neuro-immune involvement at the mucosal surfaces. Additionally, we identified delayed timing of the immune response in ducks and crows following infection with the more deadly H5N1 strain, which may account for the higher mortality in these species caused by this strain. Lastly, we identified candidate genes with potential roles in susceptibility/resistance which provide excellent targets for future research. This study has helped elucidate the responses underlying susceptibility to H5N1 influenza in avian species, which will be critical in developing sustainable strategies for future control of HPAI in domestic poultry.
AB - Highly pathogenic avian influenza (HPAI) viruses, such as H5N1, continue to pose a serious threat to animal agriculture, wildlife and to public health. Controlling and mitigating this disease in domestic birds requires a better understanding of what makes some species highly susceptible (such as turkey and chicken) while others are highly resistant (such as pigeon and goose). Susceptibility to H5N1varies both with species and strain; for example, species that are tolerant of most H5N1 strains, such as crows and ducks, have shown high mortality to emerging strains in recent years. Therefore, in this study we aimed to examine and compare the response of these six species, to low pathogenic avian influenza (H9N2) and two strains of H5N1 with differing virulence (clade 2.2 and clade 2.3.2.1) todetermine how susceptible and tolerant species respond to HPAI challenge. Birds were challenged in infection trials and samples (brain, ileum and lung) were collected at three time points post infection. The transcriptomic response of birds was examined using a comparative approach, revealing several important discoveries. We found that susceptible birds had high viral loads and strong neuro inflammatory response in the brain, which may explain the neurological symptoms and high mortality rates exhibited following H5N1 infection. We discovered differential regulation of genes associated with nerve function in the lung and ileum, with stronger differential regulation in resistant species. This has intriguing implications for the transmission of the virus to the central nervoussystem (CNS) and may also indicate neuro-immune involvement at the mucosal surfaces. Additionally, we identified delayed timing of the immune response in ducks and crows following infection with the more deadly H5N1 strain, which may account for the higher mortality in these species caused by this strain. Lastly, we identified candidate genes with potential roles in susceptibility/resistance which provide excellent targets for future research. This study has helped elucidate the responses underlying susceptibility to H5N1 influenza in avian species, which will be critical in developing sustainable strategies for future control of HPAI in domestic poultry.
KW - avian influenza
KW - transcriptome
KW - disease resistance
KW - HPAI
KW - chicken
KW - duck
KW - crow
KW - pigeon
U2 - 10.3389/fcimb.2023.1067993
DO - 10.3389/fcimb.2023.1067993
M3 - Article
SN - 2235-2988
VL - 13
SP - 1
EP - 17
JO - Frontiers in Cellular and Infection Microbiology
JF - Frontiers in Cellular and Infection Microbiology
ER -