Mutations that confer genetic stability to additional genes in influenza viruses

A method comprising administering to an avian or a mammal a composition comprising an amount of an isolated recombinant influenza virus having PA, PB1, PB2, NP, NS, M, NA, and HA viral segments, wherein at least one of the viral segments is a PA viral segment encoding PA with a residue at position 443 that is not arginine, a PB1 viral segment encoding PB1 with a residue at position 737 that is not lysine, a PB2 viral segment encoding PB2 with a residue at position 25 that is not valine or a residue at position 712 that is not glutamic acid, a NS viral segment encoding a NS1 with a residue at position 167 that is not proline, a HA viral segment encoding a HA with a residue at position 380 that is not threonine, or any combination thereof, wherein the recombinant influenza virus has enhanced replication relative to a corresponding recombinant influenza virus with a residue at position 443 in PA that is arginine, a residue at position 737 in PB1 that is lysine, a residue at position 25 in PB2 that is valine, a residue at position 712 in PB2 that is glutamic acid, a residue at position 167 in NS1 that is proline, or a residue at position 380 in HA that is threonine, wherein the position 443 in the PA corresponds to position 443 in a PA encoded by SEQ ID NO:1, wherein the position 737 in the PB1 corresponds to position 737 in a PB1 encoded by SEQ ID NO:2, wherein the position 25 or 712 in the PB2 corresponds to position 25 or 712 in a PB2 encoded by SEQ ID NO:3, or wherein the position 167 in the NS1 corresponds to position 167 in a NS1 encoded by SEQ ID NO:6, or wherein the position 380 in the HA corresponds to position 380 in a HA encoded by SEQ ID NO:7.