Prion protein protects mice from lethal infection with influenza A viruses

摘要: The cellular prion protein, designated PrPC, is a membrane glycoprotein expressed abundantly in brains and to lesser extent other tissues. Conformational conversion of PrPC into the amyloidogenic isoform key pathogenic event diseases. However, physiological functions remain largely unknown, particularly non-neuronal Here, we show that lung epithelial cells, including alveolar type 1 2 cells bronchiolar Clara cells. Compared with wild-type (WT) mice, PrPC-null mice (Prnp0/0) were highly susceptible influenza A viruses (IAVs), higher mortality. Infected Prnp0/0 lungs severely injured, inflammation apoptosis contained reactive oxygen species (ROS) than control WT lungs. Treatment ROS scavenger or an inhibitor xanthine oxidase (XO), major ROS-generating enzyme IAV-infected lungs, rescued from lethal infection IAV. Moreover, transgenic for PrP deletion Cu-binding octapeptide repeat (OR) region, Tg(PrPΔOR)/Prnp0/0 also IAV infection. These results indicate has protective role against IAVs through OR region by reducing infected Cu content activity anti-oxidant Cu/Zn-dependent superoxide dismutase, SOD1, lower It thus conceivable maintain regulate SOD1 thereby eventually protecting them IAVs. Our current highlight protection infection, suggest might be novel target molecule anti-influenza therapeutics.