Frontiers in Microbiology (Jun 2020)

Characterization and Evolutionary Analysis of a Novel H3N2 Influenza A Virus Glycosylation Motif in Southern China

  • Zhiqi Zeng,
  • Lee-Fong Yau,
  • Zengxian Lin,
  • Xuanzi Xia,
  • Zifeng Yang,
  • Zifeng Yang,
  • Jing-Rong Wang,
  • Wenjun Song,
  • Wenjun Song,
  • Xinhua Wang,
  • Xinhua Wang

DOI
https://doi.org/10.3389/fmicb.2020.01318
Journal volume & issue
Vol. 11

Abstract

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An influenza A (H3N2) virus epidemic occurred in China in 2017 and the causative strain failed to bind red blood cells (RBCs), which may affect receptor binding and antibody recognition. The objective of this study was to analyze the genetic characteristics and glycosylation changes of this novel H3N2 strain. We directly sequenced the hemagglutinin (HA) genes of H3N2 clinical specimens collected from patients with acute respiratory tract infection during 2017 in Guangdong, China. We aligned these sequences with those of A/Hong Kong/1/1968 (H3N2) and A/Brisbane/10/2007 (H3N2). Glycosylation changes were analyzed by C18 Chip-Q-TOF-MS. A/China/LZP/2017 (H3N2) was negative by HA assay, but was positive by quantitative real-time Polymerase Chain Reaction (qPCR) and direct immunofluorescence assay (DFA). We found that the HA1 residue 160T of A/China/LZP/2017 (H3N2) could block virus binding to receptors on RBCs. Furthermore, the ASN (N)-X-Thr (T) motif at HA1 residues 158–160, encoding a glycosylation site as shown by C18 Chip-Q-TOF-MS, predominated worldwide and played a critical role in RBC receptor binding. Ten glycoforms at HA1 residue 158 were identified [4_3_1_0, 5_6_0_1, 3_3_0_1, 4_4_3_0, 6_7_0_0 (SO3), 3_6_2_0, 4_3_1_2 (SO3), 7_5_2_0 (SO3), 3_6_2_1 (SO3), and 3_7_0_2]. Glycosylation changes at HA1 residues 158–160 of a circulating influenza A (H3N2) virus in Guangdong, China, in 2017 blocked binding to RBC receptors. Changes to these HA1 residues may have reduced protective antibody responses as well. Understanding these critical epitopes is important for selecting vaccine strains.

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