Modulation of fatty acid metabolism during influenza A infection
Pombo, J.P.1, Sanyal, S.1,2*,
1HKU-Pasteur Research Pole, School of Public Health, LKS Faculty of Medicine, The University
of Hong Kong, Hong Kong SAR; 2School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR
Viruses co-evolve with their host cells by developing molecular strategies which enable them to bypass the cellular immune system and/or to take advantage of their host's metabolism, in order to infect and replicate more efficiently. Lipid metabolism, specifically, is targeted by several different viruses, since it can be a source of energy, as well as production of membranes, which viruses can exploit during their replication cycle. Influenza A virus (IAV) causes seasonal epidemics worldwide, and has been responsible for several pandemics, generating a high global health burden every year. Vaccination against seasonal IAV strains is possible but has sub-optimal efficacy, due to a high mutation rate of the viral genome. IAV has been known to depend on its host cell's lipid composition at several steps of its life cycle; however, unlike other RNA viruses, there is no evidence so far as to whether influenza can actively modulate its host's lipid metabolic activity. Here, we show preliminary data suggesting that the fatty acid metabolic pathway is downregulated during influenza A infection in A549 lung epithelial cells. Expression levels of fatty acid synthase (FASN), the main enzyme responsible for de novo synthesis of fatty acids in mammalian cells, is expressed in significantly lower levels upon infection. Also, artificially reducing FASN activity during infection dramatically decreases production of progeny virions. These data may provide insight into new cellular antiviral mechanisms, and novel therapeutic alternatives to fight IAV.