Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Feb 28:13:1067993.
doi: 10.3389/fcimb.2023.1067993. eCollection 2023.

The molecular basis of differential host responses to avian influenza viruses in avian species with differing susceptibility

Katrina M Morris  1 , Anamika Mishra  2 , Ashwin A Raut  2 , Eleanor R Gaunt  1 , Dominika Borowska  1 , Richard I Kuo  1 , Bo Wang  1 , Periyasamy Vijayakumar  2 , Santhalembi Chingtham  2 , Rupam Dutta  2 , Kenneth Baillie  1 , Paul Digard  1 , Lonneke Vervelde  1 , David W Burt  1 , Jacqueline Smith  1
Affiliations

The molecular basis of differential host responses to avian influenza viruses in avian species with differing susceptibility

Katrina M Morris et al. Front Cell Infect Microbiol. .

Erratum in

Abstract

Introduction: 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 H5N1 varies 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) to determine how susceptible and tolerant species respond to HPAI challenge.

Methods: 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.

Results: 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 nervous system (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.

Discussion: 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.

Keywords: H5N1; avian influenza; chicken; crow; disease resistance; duck; pigeon; transcriptome.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Expression of viral genes after challenge with standard error bars. Expression determined by two methods, RT-qPCR of viral genes and viral counts from RNA-seq data. Only RT-qPCR data is available for turkey lung samples. For treatment group sample sizes see Supplementary File 1 .
Figure 2
Figure 2
Sample-sample network graph of each individual sample normalised counts. Clustering based on Pearson correlations of gene expression in each sample. Colours are based on species with and time points are pooled.
Figure 3
Figure 3
Average RNAseq read count expression of ISGs in each treatment group with Standard Error bars. Time 1, 2, 3 = 12h, 24h and 48h in chicken and turkey to 2.2 and 2.3 infection. Time 1, 2, 3 = 12h, 48h and 5d in the remaining treatment groups. For treatment group sample sizes see Supplementary File 1 .
Figure 4
Figure 4
Venn diagram of genes differentially expressed in lungs in each species. (A) 12h 2.2, (B) 12h, 2.3, (C) 48h 2.2, (D) 48h 2.3.
Figure 5
Figure 5
Heat map diagram of differential expression of selected nervous function genes at 12h in (A). Lung and (B). Ileum. Legend is logFC relative to control samples.
Figure 6
Figure 6
Pathway analysis comparison in (A) Lung, (B) Ileum and (C) Brain.
Figure 7
Figure 7
Pathway analysis of crow and duck lung at (A) 12h and (B) 48h and upstream regulators at 12h (C).
See this image and copyright information in PMC

References

    1. Alders R., Awuni J. A., Bagnol B., Farrell P., de Haan H. (2014). Impact of avian influenza on village poultry production globally. EcoHealth 11, 63–72. doi: 10.1007/s10393-013-0867-x - DOI - PubMed
    1. Alexander D. J., Brown I. H. (2009). History of highly pathogenic avian influenza. Sci. Tech. Rev. 28, 19–38. doi: 10.20506/rst.28.1.1856 - DOI - PubMed
    1. Attardi L. D., Reczek E. E., Cosmas C., Demicco E. G., McCurrach M. E., Lowe S. W., et al. . (2000). PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family. Genes Dev. 14, 704–718. doi: 10.1101/gad.14.6.704 - DOI - PMC - PubMed
    1. Balasubramaniam V. R. M. T., Wai T. H., Omar A. R., Othman I., Hassan S. S. (2012). Cellular transcripts of chicken brain tissues in response to H5N1 and Newcastle disease virus infection. Virol. J. 9, 53. doi: 10.1186/1743-422X-9-53 - DOI - PMC - PubMed
    1. Borowska D., Kuo R., Bailey R. A., Watson K. A., Kaiser P., Vervelde L., et al. . (2019). Highly multiplexed quantitative PCR-based platform for evaluation of chicken immune responses. PloS One 14, e0225658. doi: 10.1371/journal.pone.0225658 - DOI - PMC - PubMed

Publication types