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  2. Efficient airborne transmission of influenza D virus in ferret models and serological evidence of human exposure in Northeast China

Efficient airborne transmission of influenza D virus in ferret models and serological evidence of human exposure in Northeast China

  • Emerg Microbes Infect. 2025 Dec;14(1):2564308. doi: 10.1080/22221751.2025.2564308.
Hongbo Gao 1 Weiyang Sun 1 Pengyang Lu 2 Zhipeng Dong 2 Jiajing Wu 1 Yuanguo Li 1 Wentao Wan 3 Yue Feng 3 Bingshuo Qian 4 Mingzhu Zhang 5 Yafei Wu 5 Chunling Dong 6 Beilei Shen 1 Tiecheng Wang 1 Xianzhu Xia 1 Jie Zhang 6 Wuchun Cao 5 Yuwei Gao 1
Affiliations

Affiliations

  • 1 Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun, People's Republic of China.
  • 2 Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng, People's Republic of China.
  • 3 College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, People's Republic of China.
  • 4 School of Pharmacy, Henan University, Kaifeng, People's Republic of China.
  • 5 State Key Laboratory of Pathogen and Biosecurity, Beijing, People's Republic of China.
  • 6 Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, People's Republic of China.
Abstract

Newly emerging influenza D virus (IDV), first identified in swine in 2011, has demonstrated broad mammalian tropism with notable prevalence in bovine populations and occupational exposure-associated seroprevalence among cattle workers. This zoonotic expansion raises concerns that IDV could acquire capability for human-to-human transmission via sustained evolving in mammal hosts. Here, we evaluated the infectivity and transmissibility of a currently circulating IDV strain, D/bovine/Jilin/HY11/2023 (abbreviated as D/HY11), isolated from cattle in Northeast China in 2023. D/HY11 was able to replicate efficiently in human primary respiratory epithelial cells and exhibits respiratory tract tropism in mammals. More importantly, we found that D/HY11 could efficiently transmit through the air between ferret models (5/6). Serological surveillance (2020-2024) revealed alarming exposure rates, with no significant difference in positivity between rural and urban populations: 73.37% (449/612) in the general population and an even higher rate of 96.67% (58/60) among individuals with respiratory symptoms. The extraordinary high IDV seropositivity among people in Northeast China highlights the possibility of silent spread in mammals with mild symptoms. Among generic anti-influenza drugs tested in vitro, only polymerase inhibitors demonstrated effective suppression of IDV replication. And the D/HY11 strain exhibited enhanced polymerase activity compared to the classical IDV strain, with preliminary evidence implicating the P3 gene as a potential contributing factor to this functional enhancement. Our pathogenetic and serological findings indicate that IDV may have acquired the capacity for human-to-human transmission during its ongoing evolution, and currently circulating IDV strains already pose a potential panzootic threat.

Keywords

Influenza D virus; airborne transmission; drug susceptibility; seropostivity; silent spread.

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