Table 3.

Multiple host-adaptive mutations in viral polymerases and nucleoprotein of GsGd lineage H5N1 HPAI virus isolated from bald eagle and chicken (+ = present; − = absent). Relevant references are provided for influenza A viruses.

		Species involved
Proteins	Amino acid mutation	Bald eagle	Chickens	Predicted activity	References
PB2	K389R	+	+	↑Polymerase activity in mammalian cells	Yamayoshi et al. (2014); Yamayoshi et al. (2018)
	K482R	+	+	↑Polymerase activity in mammalian cells	Yamayoshi et al. (2014); Yamayoshi et al. (2018)
	V598T	+	+	↑polymerase activity & ↑replication in mammalian and avian cells ↑Virulence in mice	Xiao et al. (2016)
PB1	D3V	+	+	↑Polymerase activity & ↑replication in mammalian and avian cells	Elgendy et al. (2017)
	D622G	+	+	↑Polymerase activity in mammalian cells ↑Virulence in mice	Feng et al. (2016)
PA	S37A	+	+	↑Polymerase activity mammalian cells	Yamayoshi et al. (2014)
	P190S	+	+	↓Virulence in mice	DesRochers et al. (2016)
	N383D	+	+
	N409S	+	+	↑Polymerase activity & ↑replication in mammalian cells	Yamayoshi et al. (2014)
NP	M105V	+	−	↑Virulence in chickens	Tada et al. (2011a, 2011b)
	A184K	+	+	↑Replication in avian cells ↑Virulence in chickens ↑IFN response	Wasilenko, Sarmento, and Pantin-Jackwood (2009)
	N319K	+	−	↑Polymerase activity and replication in mammalian cells	Gabriel et al. (2005, 2008)