Table 1. Summary of amino acid substitutions in Cambodian A(H9N2) viruses associated with an increase in viral fitness.

Protein	Phenotype	Mutation/Motif	Residues for Cambodian Isolates (%)	References
PB2	Increased polymerase activity and replication in mammalian cell lines, increase virulence in mice	A588V	V (2)	[61]
		V598T	T (44)	[62]
		Q591K	K (5)	[63]
		E627K	E (100)	[64,65]
		D701N	D (100)	[65]
PB1	Increased polymerase activity and virulence in mice	D622G	G (100)	[66]
PB1-F2	Truncations to the 90 aa protein increase AIV pathogenicity in chickens	90aa	90aa (95)	[67]
			76aa (2)
			8aa (3)
PA	Increased polymerase activity and replication in mammalian cell lines, increased virulence in mice	V63I	I (100)	[68]
		K356R	R (2)	[69]
PA-X	Full length PA-X increases A(H9) virulence in mice	252aa	252aa (100)	[70]
HA	Multibasic cleavage site can increase viral pathogenicity	Mono-basic	PSKSSR/GLF (86)	[71,72]
			PSRSSR/GLF (14)
	Increased specificity for α2,6 human-type receptors	D101N	N (98)	[73]
		I155T*	T (100)	[74]
		S158N	N (36)	[75]
		E/T190V	V (9)	[76]
		N248D	D (3)
		R496K*	K (100)	[77]
	Increased specificity for α2,6 human-type receptors, enhanced replication in mammalian cells and ferrets, enhanced contact transmission in ferrets	Q226L	L (100)	[78,79]
NP	Increased virulence in chickens	M105V	V (91)	[80]
M1	Increased virulence in mice, chickens and ducks	I43M	M (100)	[81]
	Increased virulence in mice	T139A	A (100)	[82,83]
M2	Increased resistance to amantadine and rimantadine	S31N	N (41)	[84]
NS1	Decreased antiviral response and increased virulence in mice	P42S	S (100)	[85]
	Decreased interferon response and increased virulence in chickens	V149A	A (100)	[86]

* Amino acid (aa) mutations where the phenotype is produced only when in combination with other mutations