The viroporin M2 is present in all influenza viruses. In IAV, M2 mainly serves as a proton channel . Acting as a regulator of pH across the viral membrane, and also across the trans-Golgi membrane of infected cells, M2 is critical to IAV replication . Interestingly, co-expression of M2 and HA increases the retention of HA within the ER, although curiously with no evidence of UPR activation. Blocking M2 activity with the ion channel blocker amantadine reverses this effect . Thus, equilibration of pH between the cytoplasm and the Golgi by the M2 ion channel protein inhibits intracellular transport of viral membrane glycoproteins such as HA from the ER to the Golgi. Expression of another putative influenza viroporin, PB1-F2, from highly pathogenic avian H5N1 IAV in chickens attenuates virulence and downregulates entire gene clusters associated with the ER stress pathway, with the exception of ERN1, which encodes IRE1⍺ . The extent to which this is applicable to typical human IAV infections is unknown, although in mammalian systems PB1-F2 contributes to, rather than attenuates, pathogenesis and virulence . This may in part be attributable to varied expression of PB1-F2 across different viral isolates .