NPC1 and Niemann-Pick disease: To address the issue of whether blocked LE/L cholesterol egress acts as a cellular restriction factor for IAV replication independently of the IFN/IFITM3 axis, we induced LE/L cholesterol accumulation either through pharmacological inhibition of the LE/L cholesterol transporter NPC1, the protein affected in Niemann-Pick disease, or via overexpression of the LE/L cholesterol balancing protein annexin A6 (AnxA6), which results in a phenotype reminiscent of NPC1 deficiency (reviewed in reference 14).