Duck innate immune responses to high and low pathogenicity H5 avian influenza viruses.
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ABSTRACT: Ducks are the reservoir host of influenza A viruses, and are permissive for replication of most strains, yet can elicit robust innate immune responses to highly pathogenic strains. Tissue tropism and viral amino acid differences affect virulence, but we have limited knowledge about how viral differences influence the host innate immune response. Here we compare the innate immune response in Pekin ducks to a recombinant highly-pathogenic avian influenza (HPAI) H5N1 virus and a naturally arising attenuated variant of this strain that differs at one amino acid in polymerase A (T515A), as well as ducks infected with two different H5 strains of low pathogenic avian influenza (LPAI). Using qPCR we examined the relative abundance of transcripts for RIG-I and interferon-beta (IFN?), and downstream interferon stimulated genes (ISGs). The polymerase PA (T515A) mutation did not significantly affect replication in vivo but greatly attenuated host interferon responses. ISG induction was robust for both H5N1 strains, but was three times lower for the PA mutant strain. Low pathogenic viruses elicited detectable induction of RIG-I, IFN? and ISGs in lung and intestine tissues that correlated with the recovery of viruses from tracheal or cloacal swabs. Several genes in the MAVS signaling pathway were also upregulated by H5N1, which contributed to further amplification of the signal. We also examined hematoxylin-eosin stained tissue sections and observe evidence of lung pathology and splenocyte depletion with both H5N1 viruses at 3 dpi, and recovery by 6 dpi. However, for both H5N1 strains we observed inflammation around neurons in brain, with increased cytokine expression in some individuals. Our findings reveal HPAI H5N1 viruses induced stronger innate immune responses to the infection, while LPAI viruses elicit a milder response.
SUBMITTER: Fleming-Canepa X
PROVIDER: S-EPMC6365012 | biostudies-literature | 2019 Jan
REPOSITORIES: biostudies-literature
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