Table 3. Mammalian adaptation markers (Mertens et al., 2013) in the amino acid sequences of Av1955.

Mammalian adapt. marker mutation		Amino acid at the marker siteb								Phenotypec
		Isolates in 2013–2014d			Viruses with the highest identityd
Protein	Mutationa	Av39	Av240	Av154	Eg20616	Av1210	Spg119	Av1534	Av1955
PB2	T63I	I	I	I	I	I	I	I	I	[1]
	L89V	V	V	V	V	V	V	V	V	[1], [2]
	G309D	D	D	D	D	D	D	D	D	[1], [2]
	R318K	R	R	R	R	R	R	R	K	[2]
	T339K	K	T	T	A	T	K	T	K	[1], [2]
	Q368R	R	R	Q	R	Q	R	Q	R	[1], [2]
	H447Q	Q	Q	Q	Q	Q	Q	Q	Q	[1], [2]
	R477G	G	G	G	G	G	G	G	G	[1], [2]
	I495V	V	V	V	V	V	V	V	V	[1], [2]
	K526R	K	R	K	R	K	K	K	K	[2], [3]
	V667I	I	V	V	V	V	V	V	V	[4]
	A676T	T	T	T	T	T	T	T	T	[2], [3]
	K702R	R	K	K	K	K	R	K	R	[4]
	Subtotal	11	9	6	10	7	10	6	11
PB1	A3V	V	V	V	V	V	V	V	V	[1], [2]
	L13P	P	P	P	P	P	P	P	P	[1], [2], [5]
	R207K	K	R	K	K	K	K	K	K	[2]
	K328N	N	N	N	N	N	N	N	N	[2]
	S375N	N	N	N	N	N	S	N	N	[1], [2], [5]
	H436Y	Y	Y	Y	Y	Y	Y	Y	Y	[1], [2]
	L473V	V	V	V	V	V	V	V	V	[2]
	M677T	T	T	T	T	T	T	T	T	[1]
	Subtotal	8	7	8	8	8	7	8	8
PA	H266R	R	R	R	R	R	R	R	R	[2], [3]
	A404S	A	A	S	S	S	S	S	S	[5]
	S/A515T	T	T	T	T	T	T	T	T	[2], [3]
	Subtotal	2	2	3	3	3	3	3	3
HA	D94N	D	S	N	N	N	N	N	N	[6], [7]
	S133A	G	S	A	A	A	A	A	A	[6]
	Q/H/I138L/N	G	L	Q	Q	Q	Q	Q	Q	[1]
	I151T	T	I	I	I	I	I	I	I	[6]
	N154D	G	N	D	N	N	S	N	G	[4]
	S155N	S	S	N	N	N	N	N	N	[2], [6]
	T156A	T	T	A	A	A	A	A	A	[4], [6]
	T188I	T	T	T	T	I	T	I	T	[6]
	K189S/R	N	M	R	K	R	K	R	K	[2], [6]
	V210I	I	V	V	V	V	V	V	V	[6]
	A263T	S	A	T	T	T	T	T	T	[1]
	Subtotal	2	1	7	5	6	5	7	5
M1	V15I/T	V	I	I	I	I	I	I	I	[1]
	N30D	D	D	D	D	D	D	D	D	[1]
	T215A	A	A	A	A	A	A	A	A	[1]
	Subtotal	2	2	3	3	3	3	3	3
M2	L55F	F	L	L	L	L	L	L	L	[4]
	Subtotal	1	0	0	0	0	0	0	0
NS1	A/P42S	S	S	S	S	S	S	S	S	[1], [8]
	D87E	D	D	E	D	E	E	E	E	[1]
	T/D92E	E	E	E	E	E	E	E	E	[1]
	L98F	F	F	F	F	F	F	F	F	[1]
	I101M	M	M	M	M	M	M	M	M	[1]
	T127N	N	A	T	A	T	T	T	T	[1]
	V149A	A	A	A	A	A	A	A	A	[1], [8]
	N200S	S	G	D	G	S	S	G	S	[9]
	P215T	P	P	P	P	P	P	P	T	[5]
	Subtotal	7	5	6	5	7	7	6	8
NS2	T48A	A	A	T	A	A	A	A	A	[8]
	Subtotal	1	1	0	1	1	1	1	1
Total		34	27	33	35	35	36	34	39

Notes:

^aH5 numbering.

^bBold and underlined indicate the mammalian adaptation markers. Bold, underlined, and italic indicate the mammalian adaptation markers on the genome segment donor.

^c[1], Pathogenic in mice, increased virulence in mammals; [2], increased polymerase activity, increased replication in mammals; [3], increased virulence in mammals and birds; [4], enhanced transmission, airborne transmissibility in mammals; [5], human host marker; mammalian host marker; [6], increased virus binding to α2,6; [7], enhanced virus fusion; [8], antagonism of IFN induction, escape of antiviral host response; [9], decreased IFN antagonism.

^dVirus short name: See Table 1 note.