PB2 627V and HA 217 sites synergistically affect the lethality of H9N2 in mice

Lingcai Zhao; Miao Tian; Xifeng Hu; Menglu Fan; Chenglin Hou; Jihui Ping

doi:10.1016/j.virs.2024.12.003

February 2025

Citation: Lingcai Zhao, Miao Tian, Xifeng Hu, Menglu Fan, Chenglin Hou, Jihui Ping. PB2 627V and HA 217 sites synergistically affect the lethality of H9N2 in mice .VIROLOGICA SINICA, 2025, 40(1) : 35-49. http://dx.doi.org/10.1016/j.virs.2024.12.003

PB2 627V and HA 217 sites synergistically affect the lethality of H9N2 in mice

cstr: 32224.14.j.virs.2024.12.003

MOE Joint International Research Laboratory of Animal Health and Food Safety, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China

Corresponding author: Jihui Ping, jihui.ping@njau.edu.cn
Received Date: 15 September 2024
Accepted Date: 16 December 2024
Available online: 17 December 2024

Abstract

The H9N2 subtype avian influenza virus (AIV) continues to propagate and undergo evolution within China, thereby posing a significant threat to the poultry industry. This study encompassed the collection of 436 samples and swabs in East China over the period spanning 2018 to 2019, from which 31 strains of the H9N2 subtype viruses were isolated and purified. We revealed that the HA and NA genes of the 31 isolates categorized within the Y280 branch, while the PB2 and M genes were associated with the G1 branch, and the remaining genes aligned with the F/98 branch. Despite this alignment, antigenic mapping demonstrated differences between the 2018 and 2019 strains, with the early vaccine strains displaying low serological reactivity toward these isolates. Notably, the CK/SH/49/19 isolate exhibited lethality in mice, characterized by a PB2 E627V mutation and a HA deletion at amino acid position 217. Mechanistically, in vitro studies showed that the influenza virus CK/SH/49/19 carrying PB2 627V and HA 217M mutations displayed enhanced replication capacity, attributed to the heightened activity of the polymerase with PB2 627V. Moreover, the absence of the amino acid at the HA 217 site obstructed viral adsorption and internalization, resulted in lower activation pH, and impeded the virus budding process. Critically, in vivo experiments revealed that CK/SH/49/19 (PB2 627V, HA 217Δ) triggered a robust activation of interferon response and interferon-stimulated genes. This study furnished a theoretical foundation for the scientific prevention and control strategies against H9N2 subtype avian influenza.
- Avian influenza virus (AIV)
- , H9N2
- , PB2 627V
- , HA 217M
- , Pathogenicity

Electronic Supplementary Material

10.1016j.virs.2024.12.003-ESM2.xlsx
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10.1016j.virs.2024.12.003-ESM1.docx
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