Effect of influenza B virus on nutrient transport in cultured epithelial cells

The possibility that influenza virus could induce changes in membrane permeability to nutrients ordinarily concentrated within the cell was examined. Madin-Darby canine kidney cells were infected with egg-grown influenza B virus at 37°C and pH 7.4 (a condition in which influenza virus enters cells by endocytosis). Control cells were mock-infected with allantoic fluid from chick embryos. Transport of phosphate, 2-deoxyglucose, and α-aminoisobutyric acid was measured at various intervals, 0 to 10 hours after infection. Uptake of α-aminoisobutyric acid and phosphate by infected cells was inhibited at 2 hours as compared with controls, whereas at 6 to 10 hours, the uptake of all nutrients was higher in infected cells. Infected cells preloaded with phosphate or 2-deoxyglucose did not demonstrate increased release of these nutrients. Thus, the virally induced inhibition of uptake early in infection is not a consequence of loss of membrane integrity. Transport studies were also performed in cells with prebound virus exposed to pH 5.0 for 60 seconds at 37°C and then incubated at pH 7.4, at 37°C. Under these conditions, influenza A viruses are known to enter the cell membrane by fusing directly with it and to initiate cell to cell fusion as well. We demonstrated that influenza B virus also caused cell fusion under these conditions. In contradistinction to studies described above at pH 7.4, fused, infected cells demonstrated both marked release and diminished uptake of nutrients as compared with controls. We conclude that influenza B virus does have an effect on host cell membrane permeability; the type of effect seen is markedly influenced by factors known to determine mode of virus entry into the cell.