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The pH of Activation of the Hemagglutinin Protein Regulates H5N1 Influenza Virus Replication and Pathogenesis in Mice

After receptor binding and internalization during influenza virus entry, the hemagglutinin (HA) protein is triggered by low pH to undergo irreversible conformational changes that mediate membrane fusion. To investigate how mutations that alter the activation pH of the HA protein influence the fitness of an avian H5N1 influenza virus in a mammalian model, we infected C57BL/6J or DBA/2J mice and compared the replication and virulence of recombinant A/chicken/Vietnam/C58/04 (H5N1) HA-Y231H, wild-type, HA-H241Q, and HA-K582I viruses that have HA activation pH values of 6.3, 5.9, 5.6, and 5.4, respectively.

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