Tissue Specific Transcriptome Changes Upon Influenza A Virus Replication in the Duck

Abstract

Ducks are the natural host and reservoir of influenza A virus (IAV), and as such are permissive to viral replication while being unharmed by most strains. It is not known which mechanisms of viral control are globally regulated during infection, and which are specific to tissues during infection. Here we compare transcript expression from tissues from Pekin ducks infected with a recombinant H5N1 strain A/Vietnam 1203/04 (VN1203) or an H5N2 strain A/British Columbia 500/05 using RNA-sequencing analysis and aligning reads to the NCBI assembly ZJU1.0 of the domestic duck (Anas platyrhynchos) genome. Highly pathogenic VN1203 replicated in lungs and showed systemic dissemination, while BC500, like most low pathogenic strains, replicated in the intestines. VN1203 infection induced robust differential expression of genes all three days post infection, while BC500 induced the greatest number of differentially expressed genes on day 2 post infection. While there were many genes globally upregulated in response to either VN1203 or BC500, tissue specific gene expression differences were observed. Lungs of ducks infected with VN1203 and intestines of birds infected with BC500, tissues important in influenza replication, showed highest upregulation of pattern recognition receptors and interferon stimulated genes early in the response. These tissues also appear to have specific downregulation of inflammatory components, with downregulation of distinct sets of proinflammatory cytokines in lung, and downregulation of key components of leukocyte recruitment and complement pathways in intestine. Our results suggest that global and tissue specific regulation patterns help the duck control viral replication as well as limit some inflammatory responses in tissues involved in replication to avoid damage.

Concurrent loss of ciliary genesWDR93andCFAP46in phylogenetically distant birds

“…While this fits the general pattern of chicken-specific loss of several immune genes, the reason remains debatable [28,88,89]. Recent studies investigating the transcriptional response to viral infection in birds reveal a complex scenario of alternative pathways that can compensate for lost genes [29,[90][91][92][93]. The gene loss in the ruff (Calidris pugnax) is consistent with the Charadriiformes order being the second most important maintenance host after anseriform birds [86,[94][95][96][97].…”

Evolution of RNA sensing receptors in birds

“…These genes are strongly enriched for the RIG-I pathway and ISGs. Our recent transcriptome analyses of ducks infected with high and low pathogenic influenza mirror these results with RIG-I pathway genes being important in both the lung and the intestine, sites of infection (Campbell et al 2021). Among the top 100 genes in the lung following infection with H5N1 are type I interferons and ISGs.…”

“…Unfortunately, duck TLR3 was not included in the direct comparisons in that study, which would have been interesting because ducks typically suffer less pathology. In Pekin ducks, TLR3 is upregulated in all tissues tested following highly pathogenic H5N1 infection in the lung, spleen and intestine (Campbell et al 2021). Muscovy ducks infected with an H5N1 strain showed upregulation of TLR3 in the brain, but not in the spleen or lungs (Jiao et al 2012).…”

Concurrent loss of ciliary genes WDR93 and CFAP46 in phylogenetically distant birds

“…While this fits the general pattern of chicken-specific loss of immune genes, the reason remains debatable [ 30 , 100 , 101 ]. Recent studies investigating the transcriptional response to viral infection in birds reveal a complex scenario of alternative pathways that can compensate for lost genes [ 31 , 102 – 105 ]. Nonetheless, the WDR93 and CFAP46 gene disruption patterns suggest their loss could have functional significance for influenza infection.…”