Another viroporin, the small hydrophobic non-structural (NS) 2B protein of RV-16, is associated with non-canonical UPR activation . The NS2B proteins of many enteroviruses are Ca 2+ selective and help trigger viral release by increasing free Ca 2+ concentrations . RV-16 infection and NS2B expression both induce phosphorylation of PERK and proteolysis of ATF6 . Rather interestingly, although Ca 2+ release from the ER initiates both PERK and ATF6, IRE1 is not induced, and is in fact inhibited, both during infection and 2B expression . Accessory proteins can also inhibit the UPR. PERK phosphorylation is inhibited in IAV infection, though the mechanism is not clear . However, the IAV NS1, an RNA-binding protein and inhibitor of host IFN response, can inhibit the PERK pathway; through dsRNA binding it inhibits PKR, another activator of eIF2⍺ phosphorylation . NS1 further relieves ER stress to levels beneficial to IAV replication by binding pre-mRNA processing protein CPSF30 and suppressing XBP1 . The ability of NS1 to inhibit UPR activation is thought to be specific to certain strains such as A/Puerto Rico/8/1934, in which the NS1 protein binds more strongly to CPSF30 .