Avian influenza A H5N1 virus: a continuous threat to humans

Figures & data

short-legendFigure 1

Table 1 Table 1 Human cases of H5N1 virus infection^*

Total NO. of cases (NO. of fatal cases) [Clade]
Year	Hong Kong SAR	China	Vietnam, Laos, Myanmar, Thailand	Cambodia	Indonesia	Egypt	Pakistan, Bangladesh	Turkey, Azerbaijan, Iraq	Nigeria, Djibouti	All areas
1997	18 (6)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	18 (6)
	[0]
2003	2 (1)	1 (1)	3 (3)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	3 (2)
	[1]	[7]
2004	0 (0)	0 (0)	46 (32)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	46 (32)
			[1]
2005	0 (0)	8 (5)	66 (21)	4 (4)	20 (13)	0 (0)	0 (0)	0 (0)	0 (0)	98 (43)
		[2.3.4, 2.3.4.2]	[1, 2.3.4]	[1]	[2.1, 2.1.3, 2.1.3.2]
2006	0 (0)	13 (8)	3 (3)	2 (2)	55 (45)	18 (10)	0 (0)	23 (11)	1 (0)	115 (79)
		[2.2, 2.3.4, 7]	[1]	[1]	[2.1.2, 2.1.3, 2.1.3.2]	[2.2, 2.2.1]		[2.2]	[2.2]
2007	0 (0)	5 (3)	11 (7)	1 (1)	42 (37)	25 (9)	3 (1)	0 (0)	1 (1)	88 (59)
		[2.3.4]	[2.3.4, 2.3.4.3]	[1.1]	[2.1.3.2]	[2.2.1]	[2.2]		[2.2.1]
2008	0 (0)	4 (4)	6 (5)	1 (0)	24 (20)	8 (4)	1 (0)	0 (0)	0 (0)	44 (33)
		[2.3.4]	[2.3.4.2, 2.3.4.3]	[1.1]	[2.1.3.2]	[2.2.1, 2.2.1.1]	[2.2.2]
2009	0 (0)	7 (4)	5 (5)	1 (0)	21 (19)	39 (4)	0 (0)	0 (0)	0 (0)	73 (32)
		[2.3.2.1, 2.3.4, 2.3.4.1]	[2.3.4.2]		[unknown]	[2.2.1]
2010	1 (0)	2 (1)	7 (2)	1 (1)	9 (7)	29 (13)	0 (0)	0 (0)	0 (0)	49 (24)
	[2.3.2.1]	[2.3.2.1]	[2.3.4.1, 2.3.4.2]	[1.1]	[unknown]	[2.2.1]
2011	0 (0)	1 (1)	0 (0)	8 (8)	12 (10)	39 (15)	2 (0)	0 (0)	0 (0)	62 (34)
		[2.3.2.1]		[1.1]	[2.1.3.2]	[2.2.1]	[2.2.2]
2012 (up to 29 May)	0 (0)	1 (1) [2.3.4.2]	4 (2) [1.1]	3 (3) [1.1]	6 (6) [2.1.3.2]	9 (5) [2.2.1]	3 (0)	0 (0)	0 (0)	11 (8)
Total	21 (7)	42 (28)	151 (80)	21 (19)	189 (157)	167 (60)	9 (1)	23 (11)	2 (1)	625 (364)

* Total number of cases and mortality based on data from the World Health Organization⁸ and data from Hong Kong.¹ Clade information based on Refs. 9–12.

Table 2 Table 2 Natural mutations in human isolates of the H5N1 virus that are associated with virulence or adaptation to humans. Gene information obtained from the NCBI Influenza Virus Reource,⁵⁷ sequences with duplicate strain names but different sequences were excluded from the analysis.

Amino acid mutations	Indonesia^a	Egypt^b	Vietnam, Thailand, Cambodia, Laos^c	Hong Kong, China^d
Haemagglutinin (H5 numbering)
L129V^Citation58	S=89 (86%)	S=82 (59%)	S=12 (14%)	S=41 (89%)
	L=15 (14%)	L=2 (1%)	L=69 (81%)	L=5 (11%)
	Δ=0 (0%)	Δ=56 (40%)	Δ=0 (0%)	Δ=0 (0%)
	V=0 (0%)	V=0 (0%)	V=2 (2%)	V=0 (0%)
			I=1 (1%)
129 deletion+I151T^Citation47	I=102 (98%)	I=84 (60%)	I=85 (100%)	I=45 (98%)
	T=2^e (2%)	T=56^f (40%)	T=0 (0%)	T=1^a (2%)
A134V^Citation58	A=104 (100%)	A=135 (96%)	A=75 (88%)	A=41 (89%)
	S=0 (0%)	S=1 (<1%)	V=6 (7%)	S=0 (0%)
	V=0 (0%)	V=1 (<1%)	X=3 (4%)	V=3 (7%)
	X=0 (0%)	X=3 (2%)		X=1 (2%)
	T=0 (0%)	T=0 (0%)		T=1 (2%)
139G^Citation59	G=103 (99%)	G=140 (100%)	G=84 (99%)	G=46 (100%)
	R=1 (1%)	R=0 (0%)	R=1 (1%)	R=0 (0%)
T156A (absence of glycosylation at 154–156)^Citation60,Citation61	T=104 (0%)	T=2 (1%)	T=85 (100%)	T=33 (72%)
	A=0 (%)	A=138 (99%)	A=0 (%)	A=9 (20%)
	S=0 (0%)	S=0 (0%)	S=0 (0%)	S=4 (9%)
N182K^Citation62	N=104 (100%)	N=135 (96%)	N=83 (98%)	N=46 (100%)
	K=0 (0%)	K=2 (1%)	K=0 (0%)	K=0 (0%)
	X=0 (0%)	X=3 (2%)	X=0 (0%)	X=0 (0%)
	D=0 (0%)	D=0 (0%)	D=1 (1%)	D=0 (0%)
	S=0 (0%)	S=0 (0%)	S=1 (1%)	S=0 (0%)
K189R^Citation61	K=1 (1%)	K=0 (0%)	K=79 (93%)	K=41 (89%)
	R=104 (99%)	R=138 (99%)	R=5 (6%)	R=5 (11%)
	G=0 (0%)	G=1 (<1%)	G=0 (0%)	G=0 (0%)
	S=0 (0%)	S=1 (<1%)	S=0 (0%)	S=0 (0%)
	N=0 (0%)	N=0 (0%)	N=1 (1%)	N=0 (0%)
Q192H, Q192R^Citation47,Citation62	Q=105 (100%)	Q=134 (95%)	Q=84 (99%)	Q=46 (100%)
	H=0(0%)	H=4 (3%)	H=0 (0%)	H=0 (0%)
	R=0 (0%)	R=0 (0%)	R=0 (0%)	K=0 (0%)
	K=0 (0%)	K=2 (2%)	K=0 (0%)
			X=1 (1%)
Q222L^Citation59	Q=104 (99%)	Q=140 (100%)	Q=85 (100%)	Q=46 (100%)
	L=0 (0%)	L=0 (0%)	L=0 (0%)	L=0 (0%)
	R=1 (1%)	R=0 (0%)	R=0 (0%)	R=0 (0%)
G224S^Citation59	G=105 (100%)	G=140 (100%)	G=85 (100%)	G=46 (100%)
	S=0 (0%)	S=0 (0%)	S=0 (0%)	S=0 (0%)
S235P^Citation47	S=0 (0%)	S=126 (90%)	S=0 (0%)	P=43 (93%)
	P=105 (100%)	P=14 (10%)	P=84 (99%)	S=3 (7%)
			Q=1 (1%)
PB2^g
Q591K^Citation63	Q=89 (99%)	Q=2 (100%)	Q=54 (93%)	Q=39 (100%)
	K=1 (1%)	K=0 (0%)	K=0 (0%)	K=0 (0%)
	R=0 (0%)		R=4 (7%)	R=0 (0%)
E627K^Citation63	E=80 (89%)	E=0 (0%)	E=29 (50%)	E=35 (80%)
	K=10 (11%)	K=2 (100%)	K=29 (50%)	K=9 (20%)
D701N^Citation63	D=88 (100%)	D=2 (100%)	D=50 (86%)	D=35 (85%)
	N=0 (0%)	N=0 (0%)	N=8 (14%)	N=6 (15%)

a n = 105 for haemagglutinin and n = 90 for PB2. For haemagglutinin, nucleotide information for position 129, 134, 139, 156 and 189 is available for only 104 strains; for PB2, nucleotide information for position 701 is available for only 88 strains.

b n = 140 for haemagglutinin and n = 2 for PB2.

c n = 85 for haemagglutinin and n = 58 for PB2. For haemagglutinin, nucleotide information for position 129 and 134 is available for only 84 strains.

d n = 46 for haemagglutinin. For PB2, nucleotide information is available for 39 strains at position 591, 44 strains at position 627, and 41 strains at position 701.

e S at position 129.

f Deletion at position 129.

g All strains had glutamic acid at position 158 of the PB2 gene.

World Health Organization. Cumulative number of confirmed human cases for avian influenza A(H5N1) reported to WHO, 2003–2012. Geneva: WHO, 2012. Available at http://www.who.int/influenza/human_animal_interface/EN_GIP_20120529CumulativeNumberH5N1cases.pdf (accessed 6 June 2012).

 Google Scholar

Yuen KY, Chan PK, Peiris M et al. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet1998; 351: 467–471.

 PubMed Web of Science ®Google Scholar

Bao Y, Bolotov P, Dernovoy D et al. The influenza virus resource at the National Center for Biotechnology Information. J Virol2008; 82: 596–601.

 PubMed Web of Science ®Google Scholar

Auewarakul P, Suptawiwat O, Kongchanagul A et al. An avian influenza H5N1 virus that binds to a human-type receptor. J Virol2007; 81: 9950–9955.

 PubMed Web of Science ®Google Scholar

Watanabe Y, Ibrahim MS, Ellakany HF et al. Acquisition of human-type receptor binding specificity by new H5N1 influenza virus sublineages during their emergence in birds in Egypt. PLoS Pathog2011; 7: e1002068.

 PubMed Web of Science ®Google Scholar

Medina RA, Garcia-Sastre A. Influenza A viruses: new research developments. Nat Rev Microbiol2011; 9: 590–603.

 PubMed Web of Science ®Google Scholar

Gao Y, Zhang Y, Shinya K et al. Identification of amino acids in HA and PB2 critical for the transmission of H5N1 avian influenza viruses in a mammalian host. PLoS Pathog2009; 5: e1000709.

 PubMed Web of Science ®Google Scholar

Stevens J, Blixt O, Chen LM, Donis RO, Paulson JC, Wilson IA. Recent avian H5N1 viruses exhibit increased propensity for acquiring human receptor specificity. J Mol Biol2008; 381: 1382–1394.

 PubMed Web of Science ®Google Scholar

Yamada S, Suzuki Y, Suzuki T et al. Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors. Nature2006; 444: 378–382.

 PubMed Web of Science ®Google Scholar

Yamada S, Hatta M, Staker BL et al. Biological and structural characterization of a host-adapting amino acid in influenza virus. PLoS Pathog2010; 6: e1001034.

 PubMed Web of Science ®Google Scholar