TABLE 1.

Serial passage of A(H5N1) viruses in the presence of increasing concentrations of oseltamivir^a

Virus strain	Passage no.	Oseltamivir concn	Zanamivir IC50	Oseltamivir IC50	HA mutationb	NA mutation (%)c
A/Vietnam/1203/2004		0 nM	0.5	0.2
	1	1 nM	0.7	0.3
	2	5 nM	0.5	0.3
	3	25 nM	0.3	0.2
	4	50 nM	0.3	0.2
	5	250 nM	0.5	0.2
	6	1,250 nM	0.5	25.3		H274Y (64)
	7	6,250 nM	0.5	145.2		H274Y (92)
	8	31 μM	0.5	177.0		H274Y (100)
	9	156 μM	0.5	180.3	A45S; K156E; P210Q; L313F	H274Y (100)
	10	781 μM	0.5	152.8	A45S; K156E; P210Q; L313F	H274Y (100)
A/Chicken/Laos/26/2006		0 nM	0.3	0.3
	1	1 nM	0.3	0.2
	2	5 nM	0.3	0.3
	3	25 nM	0.3	0.3
	4	125 nM	0.3	0.3
	5	625 nM	0.3	0.4
	6	3,125 nM	0.3	0.4		I222M (68)
	7	16 μM	0.3	18.2	K234Q	I222M (65)
	8	78 μM	0.4	89.2	K234Q	I222M (31); H274Y (45)
	9	390 μM	0.5	191.6	K234Q	I222M (21%); H274Y (100)
	10	1,950 μM	0.7	1,390.0	K234Q	I222M (70); H274Y (100)

^aA(H5N1) influenza viruses A/Vietnam/1203/2004 and A/Chicken/Laos/26/2006 were cultured in MDCK cells in the presence of increasing concentrations of oseltamivir. Each passage level was tested for susceptibility to zanamivir and oseltamivir and sequenced to investigate the generation of any HA or NA mutations. IC₅₀ values are based on assays completed in duplicate.

^bBased on H5 residue numbering.

^cBased on N2 residue numbering. The percentages in parentheses indicate the proportion of each individual mutant in the total viral population based on pyrosequencing analysis. Mutations that were present at <20% of the total viral population are not shown.