Abstract Title
An emerging PB2-627 polymorphism increases the pandemic potential of avian influenza virus by breaking through ANP32 host restriction in mammalian and avian hosts
Abstract
The PB2-E627K mutation is a key factor for avian influenza virus (AIV) to break through interspecies limitations and cause mammalian infections. So far, PB2-E627K has not been maintained in AIV in poultry, which limits the spread of AIVs from avian to humans. Here, we show that an independent cluster with PB2-627V has emerged in 2010s, which is prevalent in various avian, mammalian, and human isolates of AIVs, including H9N2, H7N9, H3N8, and 2.3.4.4b H5N1 subtypes. To assess whether PB2-627V overcomes host restrictions and poses a risk for human pandemics, we systematically assessed its host adaptation, fitness, and transmissibility across three subtypes of AIVs (H9N2, H7N9, and H3N8) in different host models, including avian and human cells, chickens, mice, and ferrets-species where infections naturally occur. We found that unlike PB2-627E or PB2-627K, PB2-627V facilitates AIVs to efficiently infect, replicate, and passage in chickens and mice by utilizing both avian- and human-origin ANP32A proteins. Importantly, and like PB2-627K, PB2-627V promotes efficient transmission between ferrets through respiratory droplets. Deep sequencing indicates that PB2-627V remains stable during virus infection and transmission in different hosts. Our study highlights AIV variants with this dual adaptive PB2-627V are capable of crossing the avian-to-human barrier. Their prevalence in poultry raises the chances of human exposure to AIVs, which may significantly amplifying the risk of pandemics.
Co-Author(s)
Author: Yuxin Guo,1 Sicheng Shu,1 Yong Zhou,1 WenJing Peng,1 ZhiMin Jiang,1 Yudong Li,1 Tian Li,1 Linlin Wang,1 Xue Chen,1 Jinze Dong,1 Chuankuo Zhao,1 Fanshu Du,1 Maggie Haitian Wang, 4,5 Yipeng Sun,1 Honglei Sun,1 Kin-Chow Chang,2 Hui-Ling Yen,3 Jinhua. Liu,1, Juan Pu,1,6
Affiliations:
1. National Key Laboratory of Veterinary Public Health and Safety, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
2. School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK
3. School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
4. Centre for Clinical Research and Biostatistics, JC School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong SAR, China.
5. CUHK Shenzhen Research Institute, Shenzhen, China.
Abstract Category
Avian influenza in mammals, pandemic preparedness, and one health