Metabolic effects of influenza virus infection in cultured animal cells: Intra- and extracellular metabolite profiling

For most metabolites the comparison of infected (human influenza A/PR/8/34) and mock-infected cells showed a very similar behavior during the first 10-12 h post infection (pi). Significant changes were observed after about 12 h pi: (1) uptake of extracellular glucose and lactate release into the cell culture supernatant were clearly increased in infected cells compared to mock-infected cells. At the same time (12 h pi) intracellular metabolite concentrations of the upper part of glycolysis were significantly increased. On the contrary, nucleoside triphosphate concentrations of infected cells dropped clearly after 12 h pi. This behaviour was observed for two different human influenza A/PR/8/34 strains at slightly different time points.Comparing these results with literature values for the time course of infection with same influenza strains, underline the hypothesis that influenza infection only represents a minor additional burden for host cell metabolism. The metabolic changes observed after12 h pi are most probably caused by the onset of apoptosis in infected cells. The comparison of experimental data from two variants of the A/PR/8/34 virus strain (RKI versus NIBSC) with different productivities and infection dynamics showed comparable metabolic patterns but a clearly different timely behavior. Thus, infection dynamics are obviously reflected in host cell metabolism.Yearly influenza epidemics with numerous death cases and severe economic impact demonstrate the urgent need for vaccinations against the flu. One characteristic problem for human influenza vaccination is the need for new vaccines every season because of the antigenic shift of the virus [1]. Various continuous cell lines capable of a virus replication to high titers are reported in literature [2,3]. Typically, the process consists of two stages: First, host cells are grown in bioreactors to cell numbers of 1-10 million cells per mL. Then, cells are infected with active virus, which replicates in the ce