A Single Amino Acid at Position 158 in Hemagglutinin Affects the
Antigenic Property of Eurasian Avian-like H1N1 Swine Influenza Viruses
Abstract
Influenza viruses have been posing a great threat to public health and
animal industry. The developed vaccines have been widely used to reduce
the risk of potential pandemic; however, the ongoing antigenic drift
makes influenza virus escape from host immune response and hampers
vaccine efficacy. Until now, the genetic basis of antigenic variation
remains largely unknown. In this study, we used A/swine/Guangxi/18/2011
(GX/18) and A/swine/Guangdong/104/2013 (GD/104) as models to explore the
molecular determinant for antigenic variation of Eurasian avian-like
H1N1 (EA H1N1) swine influenza viruses (SIVs), and found that the GD/104
virus exhibited 32~64-fold lower antigenic
cross-reactivity with antibodies against GX/18 virus. Therefore, we
generated polyclonal antibodies against GX/18 or GD/104 virus and a
monoclonal antibody (mAb), named mAb102-95, targeted to the
hemagglutinin (HA) protein of GX/18 virus, and found that a single amino
acid substitution at position 158 in HA protein substantially altered
the antigenicity of virus. The reactivity of GX/18 virus containing
G158E mutation with the mAb102-95 decreased 8-fold than that of the
parental strain. Contrarily, the reactivity of GD/104 virus bearing
E158G mutation with the mAb102-95 increased by 32 times as compared with
that of the parental virus. Structural analysis showed that the amino
acid mutation from G to E was accompanied with the R group changing from
-H to -(CH 2) 2-COOH. The induced steric
effect and increased hydrophilicity of HA protein surface jointly
contributed to the antigenic drift of EA H1N1 SIVs. Our study provides
experimental evidence that G158E mutation in HA protein affects the
antigenic property of EA H1N1 SIVs, and widens our horizon on the
antigenic drift of influenza virus.