Effects of a hemagglutinin D222G substitution on the pathogenicity of 2009 influenza A (H1N1) virus in mice.
The surface glycoprotein hemagglutinin (HA) of influenza virus initiates the infection process by binding to sialic acid receptors on upper respiratory cells in the host. In contrast to avian influenza viruses, which bind to sialic acids connected by an α2-3 linkage to the penultimate galactose, human influenza viruses prefer sialic acids with an α2-6 linkage. Recently, there have been multiple cases of severe human infections associated with an HA D222G mutant influenza virus. In this study, we have investigated the pathogenic effects of the HA D222G substitution in a 2009 pandemic H1N1 virus in mice. Compared with the A/Korea/01/2009 (K/09) virus, the HA D222G mutant showed reduced growth in cells and reduced binding avidity to human and turkey red blood cells. In a BALB/c mouse infection model, infection with the HA D222G mutant virus resulted in less body weight loss when compared to the parental K/09 virus. Altogether, our data suggest that the HA D222G substitution in the K/09 virus might be deleterious to viral fitness.
Department of Microbiology, College of Medicine, and the Institute for Viral Diseases, Korea University, Seoul, 136-705, Republic of Korea.
Jin Il
JI
Kim
Ilseob
I
Lee
Sehee
S
Park
Sangmoo
S
Lee
Min-Woong
MW
Hwang
Joon-Yong
JY
Bae
Jun
J
Heo
Donghwan
D
Kim
Seok-Il
SI
Jang
Jin-Won
JW
Song
Man-Seong
MS
Park
D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001835:Body Weight; D002460:Cell Line; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D057809:HEK293 Cells; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000472:pathogenicity; D007251:Influenza, Human; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000473:pathology*; D053585:Virus Attachment; D014779:Virus Replication / Q000235:genetics
C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus