Abstract
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.
Highlights
Avian influenza viruses (AIVs) are enveloped, single-stranded, negative-sense RNA viruses which belong to the Orthomyxoviridae family
Transcriptomic profiling of the CLEC213 infected by AIV
In order to finely characterize the response of CLEC213 cells to the influenza virus infection, we compared the transcriptomic profiles of infected and mock-infected cells using microarrays
Summary
Avian influenza viruses (AIVs) are enveloped, single-stranded, negative-sense RNA viruses which belong to the Orthomyxoviridae family. They can cause disease in poultry and wild birds, and in humans. In addition to economic costs, highly pathogenic (HP) AIVs are a serious threat for human health due to the capacity of certain strains to cross species barriers and cause human infections [2]. HPAIVs can replicate in a wide variety of tissues and cell types and induce severe systemic disease in chickens with very high mortality. Low pathogenic (LP) AIVs mainly replicate in epithelial tissue, principally respiratory and digestive [3]. LPAIVs cause asymptomatic to mild diseases but induce a decrease in growth performance and in egg production [3]
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