Polygenic virulence factors involved in pathogenesis of 1997 Hong Kong H5N1 influenza viruses in mice.
Virulence factors of influenza A (H5N1) viruses collected in 1997 from mammalian hosts were examined using a BALB/c mouse model. Fifteen amino acid (aa) residues in four influenza virus genes which correlated with high- and low-pathogenic phenotypes in mice were identified by analyzing sequence alignments. In addition to these specific residues, the effects of aa residue 627 of the PB2 gene, and the hemagglutinin (HA) and neuraminidase (NA) genes were also investigated using a reverse genetics system established with representative viruses of low (A/Hong Kong/486/97) and high (A/Hong Kong/483/97) pathogenicity for mice. None of 15 aa residues alone had any effect on virulence. The HA and NA genes had a synergistic effect on virulence and the absence of a glycosylation site at aa154 in the HA gene also increased virulence of virus. Multiple genes are involved in virulence of Hong Kong H5N1 influenza A viruses for mice with the presence of lysine at aa627 in the PB2 gene exhibiting a significantly larger effect than the HA and NA genes.
Chen
Hualan
H
Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road, N.E., MS-G16, Atlanta, GA 30333, USA.
Bright
Rick A
RA
Subbarao
Kanta
K
Smith
Catherine
C
Cox
Nancy J
NJ
Katz
Jacqueline M
JM
Matsuoka
Yumiko
Y
D000818:Animals; D004195:Disease Models, Animal; D006723:Hong Kong; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000401:mortality / Q000503:physiopathology / Q000821:virology*; D015678:Viral Structural Proteins / Q000737:chemistry / Q000235:genetics*; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics*
D015678:Viral Structural Proteins; D037521:Virulence Factors