Mutation of D201G near the receptor binding site significantly drive
antigenic drift of circulating H9N2 subtype avian influenza virus
Abstract
The H9N2 subtype of avian influenza virus (H9N2 AIV) has caused
significant losses in chicken flocks throughout China. Our previous
research has showed that field isolates of H9N2 underwent antigenic
drift to evolve into distinct groups with significant antigenic
divergence from the commercially available vaccines. The present study
sought to identify which single mutations that have naturally appeared
in isolates from the past 5 years has driven antigenic drift. Six
high-frequency mutation sites in/near the receptor binding site (RBS)
region were screened by comparing amino acid alignments of the H9N2 AIVs
isolated from China between 2014 and 2019. Two substitutions, (A168N and
D201G) were demonstrated to have a significant impact on the
antigenicity, but did not change the growth kinetics and cell tropism of
the virus. It is worth noting that the D201G substitution not only
significantly changed the antigenicity, but also caused immune escape of
the parental virus. In conclusion, A168N and D201G substitution are
newly discovered determinants that can significantly change the
antigenicity of H9N2 AIV, which should be tracked during outbreaks.