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Transcriptomic profiling of a chicken lung epithelial cell line (CLEC213) reveals a mitochondrial respiratory chain activity boost during influenza virus infection

Avian Influenza virus (AIV) is a major concern for the global poultry industry. Since 2012, several countries have reported AIV outbreaks among domestic poultry. These outbreaks had tremendous impact on poultry production and socio-economic repercussion on farmers. In addition, the constant emergence of highly pathogenic AIV also poses a significant risk to human health. In this study, we used a chicken lung epithelial cell line (CLEC213) to gain a better understanding of the molecular consequences of low pathogenic AIV infection in their natural host. Using a transcriptome profiling approach based on microarrays, we identified a cluster of mitochondrial genes highly induced during the infection. Interestingly, most of the regulated genes are encoded by the mitochondrial genome and are involved in the oxidative phosphorylation metabolic pathway. The biological consequences of this transcriptomic induction result in a 2.5- to 4-fold increase of the ATP concentration within the infected cells. PB1-F2, a viral protein that targets the mitochondria was not found associated to the boost of activity of the respiratory chain. We next explored the possibility that ATP may act as a host-derived danger signal (through production of extracellular ATP) or as a boost to increase AIV replication. We observed that, despite the activation of the P2X7 purinergic receptor pathway, a 1mM ATP addition in the cell culture medium had no effect on the virus replication in our epithelial cell model. Finally, we found that oligomycin, a drug that inhibits the oxidative phosphorylation process, drastically reduced the AIV replication in CLEC213 cells, without apparent cellular toxicity. Collectively, our results suggest that AIV is able to boost the metabolic capacities of its avian host in order to provide the important energy needs required to produce progeny virus.

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S1478 Oligomycin A Oligomycin A (MCH 32) is an inhibitor of ATP synthase, inhibits oxidative phosphorylation and all the ATP-dependent processes occurring on the coupling membrane of mitochondria. (46) (3)

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