Influenza Virus M2 Protein Ion Channel Activity Is Not Required to Maintain the Equine-1 Hemagglutinin in Its Native Form in Infected Cells

Abstract

The equine-1 influenza virus A/Cornell/74 (H7N7) hemagglutinin (HA) is cleaved to HA1 and HA2 in the trans Golgi network (TGN) of infected cells. The avian influenza virus A/chicken/Germany/34 (fowl plague virus Rostock) H7 HA is also cleaved to HA1 and HA2 intracellularly in the TGN. To maintain the fowl plague virus Rostock HA in its native form during transport through the TGN, a functioning M2 ion channel activity is required, otherwise the HA undergoes its transition to the low-pH form (Sugrue et al., 1990, EMBO J. 9, 3469-3476). Studies were initiated to investigate if the equine H7 HA has intracellular requirements different from those of the fowl plague virus Rostock HA. We report here that the pH of transition to the low-pH form of the equine-1 HA is ∼pH 5.3 and that the M2 protein ion channel blocker, amantadine, does not have a discernable effect on the native conformation of equine-1 HA during transport through the TGN. Moreover, the equine-1 HA expressed from cDNA does not require coexpression of a functional M2 protein to maintain HA in its native conformation.