Reduced extracellular pH reversibly inhibits oligomerization, intracellular transport, and processing of the influenza hemagglutinin in infected Madin-Darby canine kidney cells

Incubation of Madin-Darby canine kidney cells infected with influenza virus in medium of pH 5.8-6.0 blocks transport of newly synthesized hemagglutinin and processing of the hemagglutinin oligosaccharides to a form resistant to endo H digestion. Upon restoration of the culture medium to pH 7.4, arrested hemagglutinin is processed and then appears on the cell surface, indicating that exclusively transport and not oligosaccharide processing is inhibited. Based upon kinetic data and localization of blocked hemagglutinin by immunofluorescence, the point of inhibition appears to be a discrete step in transport located in a pre-Golgi compartment. This conclusion is supported by the observation that trimerization of hemagglutinin, which is believed to occur in the endoplasmic reticulum, is also inhibited by acidic medium.