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

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.

Transcriptome analysis of chicken intraepithelial lymphocyte natural killer cells infected with very virulent infectious bursal disease virus

“…Wang et al 32 had the same finding, where the mRNA levels of CCL19 were upregulated after infection with vvIBDV. Their data suggest that CCL19 acts as a chicken peripheral white blood cells (PWBC) chemotactic factor and facilitates the infiltration of PWBC into the bursa after IBDV infection 33 . Interleukins such as IL17A and IL22 , which were upregulated at 3 dpi, are important to maintain mucosal immunity against virus infection and include induction of antiviral proteins, recruitment of neutrophils to infected areas and enhancement of mucosal barrier repair.…”

Fueling influenza and the immune response: Implications for metabolic reprogramming during influenza infection and immunometabolism

“…66 Moreover, transcriptomic analysis of chicken lung epithelial cells infected with a low pathogenic H6N2 strain showed avian influenza virus increased OXPHOS. 67 Induction of energy metabolism proteins, such as ATP synthase and cytochrome b5 type A in the mitochondria, occurs during IAV infection of A549, and inhibition of OXPHOS reduces IAV replication without apparent cellular toxicity. 68,69 Taken together, these in vitro studies indicate that IAV induces changes in glycolysis, the TCA cycle, and OXPHOS in cell lines.…”

Inter-Species Host Gene Expression Differences in Response to Human and Avian Influenza A Virus Strains

“…It was suggested that activation of cellular metabolism in IAV infections was a compensatory mechanism of the cell for resources (energy, lipid, amino acids and nucleic acids) which were depleted during virion production [ 43 ]. Recently, Meyer et al, 2017 demonstrated increased expression of mitochondrial genes associated with oxidative phosphorylation in LPAI H6N2 and H7N1 viruses in a chicken lung epithelial cell line (CLEC213) [ 44 ]. The same study showed that inhibition of oxidative phosphorylation using oligomycin reduced virus replication without cell toxicity [ 44 ].…”

“…Recently, Meyer et al, 2017 demonstrated increased expression of mitochondrial genes associated with oxidative phosphorylation in LPAI H6N2 and H7N1 viruses in a chicken lung epithelial cell line (CLEC213) [ 44 ]. The same study showed that inhibition of oxidative phosphorylation using oligomycin reduced virus replication without cell toxicity [ 44 ]. Overall, the present data suggested that induction of or maintaining specific metabolic pathways during IAV infections could be important for cell survival and IAV replication.…”