Table 2.

Experimentally verified molecular markers/motifs in the neuraminidase (NA; segment 6) gene of avian influenza viruses associated with enhanced virulence and antiviral resistance

Mutation/motif (N2 numberinga)	Phenotype	Subtypes tested	References
49–68 deletionb	Enhanced virulence in mice	H5N1 (with H1N1 backbone)	[73]
			[74]
	Enhanced virulence in mice	H7N9 (human isolate)	[75]
54–72 deletion	Enhanced virulence in mice but not chickens	H5N1	[72]
	Enhanced virulence in mice	H7N9 (human isolate)	[75]
	Enhanced virulence in mice and chickens	H1N1 (avian)	[71]
54–73 deletion	Enhanced virulence in mice	H7N9 (human isolate)	[75]
54–75 deletion	Enhanced virulence in chickens but not ducks	H7N1	[76]
54–81 deletion	Enhanced replication in chicken, but not duck, cell line. Enhanced replication in respiratory tract of chickens.	H2N2	[246]
57–65 deletion	Enhanced virulence in mice	H7N9 (human isolate)	[77]
V116A	Reduced susceptibility to oseltamivir and zanamivir	H5N1	[247, 248]
I117T	Reduced susceptibility to oseltamivir and zanamivir	H5N1	[249]
E119A	Reduced susceptibility to zanamivir	H4N2	[250]
	Reduced susceptibility to oseltamivir and zanamivir	H5N1	[251, 252]
	Reduced susceptibility to oseltamivir, zanamivir, peramivir, and laninamivir	H7N9	[253]
E119D	Reduced susceptibility to zanamivir	H4N2	[250]
	Reduced susceptibility to oseltamivir, zanamivir, and peramivir	H5N1	[251]
	Reduced susceptibility to oseltamivir, zanamivir, peramivir, and laninamivir	H7N9	[253]
	Reduced susceptibility to zanamivir	H9N2	[254]
E119G	Reduced susceptibility to zanamivir	H4N2	[250]
	Reduced susceptibility to zanamivir and peramivir	H5N1	[251]
	Reduced susceptibility to zanamivir, peramivir, and laninamivir	H7N9	[253]
Q136L	Reduced susceptibility to oseltamivir and zanamivir	H5N1	[255]
	Reduced susceptibility to zanamivir, permaivir, and laninamivir	H7N9	[253]
R152K	Reduced susceptibility to laninamivir	H7N9	[253]
D198G	Reduced susceptibility to oseltamivir and zanamivir	H5N1	[256]
I222M	Reduced susceptibility to oseltamivir	H5N1	[256]
I222K	Reduced susceptibility to oseltamivir, zanamivir, peramivir, and laninamivir	H7N9	[253]
I222R	Reduced susceptibility to oseltamivir and laninamivir	H7N9	[253]
S246N	Reduced susceptibility to oseltamivir	H5N1	[248]
T247P	Reduced susceptibility to oseltamivir and zanamivir	H7N9	[253]
H274Y	Reduced susceptibility to oseltamivir and peramivir	H5N1	[251–253, 256–258]
	Reduced susceptibility to oseltamivir	H7N9	[253]
E276D	Reduced susceptibility to oseltamivir, zanamivir, peramivir, and laninamivir	H7N9	[253]
E277Q	Reduced susceptibility to oseltamivir	H5N1	[259]
R292K	Reduced susceptibility to zanamivir	H4N2	[250]
	Reduced susceptibility to oseltamivir	H6N2	[260]
	Reduced susceptibility to oseltamivir, zanamivir, peramivir, and laninamivir	H7N9	[261, 262]
	Reduced susceptibility to oseltamivir	H9N2	[254]
N294S	Reduced susceptibility to oseltamivir, zanamivir, and peramivir	H5N1	[251, 252, 257, 263]
	Reduced susceptibility to zanamivir	H7N9	[253]
R371K	Reduced susceptibility to oseltamivir, zanamivir, peramivir, and laninamivir	H7N9	[253]
A401T	Increased virus binding to α2–3	H7N9	[264]
K432T	Reduced susceptibility to zanamivir	H5N1	[265]
I117V, I314V	Reduced susceptibility to oseltamivir	H5N1	[247]
E119V, E222V	Reduced susceptibility to oseltamivir	H7N9	[266]
E119A/D/G, H274Y	Reduced susceptibility to oseltamivir, zanamivir, and peramivir	H5N1	[251]
I222L, S246N	Reduced susceptibility to oseltamivir	H5N1	[265]
I222M/V, H274Y	Reduced susceptibility to oseltamivir and peramivir	H5N1	[256]
K150N, I222L, S246N	Reduced susceptibility to oseltamivir	H5N1	[248]

Single mutations are presented first followed by motifs involving multiple mutations. Individual markers and motifs are listed in numerical order for ease of identifying mutation of interest

^aMutation/location N2 numbering relative to A/Aichi/2/1968 (H3N2)

^bDeletions are numbered according to alignments with A/Goose/Guangdong/1/1996 (H5N1)