Abstract Title
Internal genomic segments contributed to the fitness advantage and spread of the panzootic H5N1 2.3.4.4b lineage of influenza A virus
Abstract
H5N1 avian influenza has been a major threat to human and animal health since the appearance of the Goose/Guangdong high pathogenicity lineage. This threat has resurged in 2020-2021 after the emergence of novel panzootic H5NX genotypes of highly pathogenic viruses of clade 2.3.4.4b. An initial genotype rapidly spread globally, reassorting with local low pathogenicity avian influenza viruses, with novel genotypes isolated in several continents and devastating impacts in wild and domestic bird populations. The increased spread and pathogenicity of the 2.3.4.4b clade correlated with an N8 to N1 genomic segment swap, followed by several reassortment events, generating genetic diversity particularly in segments 1-3, 5 and 8.
Aiming to understand how the internal gene segments contributed to the emergence and rapid expansion of the H5N1 epizootic, reverse genetic viruses have been generated to represent the H5N8 precursor and subsequent H5N1 diversity of UK isolates, all harbouring the glycoproteins of a laboratory-adapted strain. H5N8 showed reduced viral fitness in avian cells (chicken lung epithelial cells and chicken and duck fibroblasts), compared to H5N1 viruses which correlated with PB2- and PA-dependent increased polymerase activity. Moreover, a segment 8 constelation swap resulted in improved NS1 ability to suppress cellular gene expression and subsequent reduction of type I interferon secretion.
All together, this work provides detailed context for how panzootic influenza viruses can emerge through a confluence of advantageous but complementary traits provided by the internal genomic segments.
Aiming to understand how the internal gene segments contributed to the emergence and rapid expansion of the H5N1 epizootic, reverse genetic viruses have been generated to represent the H5N8 precursor and subsequent H5N1 diversity of UK isolates, all harbouring the glycoproteins of a laboratory-adapted strain. H5N8 showed reduced viral fitness in avian cells (chicken lung epithelial cells and chicken and duck fibroblasts), compared to H5N1 viruses which correlated with PB2- and PA-dependent increased polymerase activity. Moreover, a segment 8 constelation swap resulted in improved NS1 ability to suppress cellular gene expression and subsequent reduction of type I interferon secretion.
All together, this work provides detailed context for how panzootic influenza viruses can emerge through a confluence of advantageous but complementary traits provided by the internal genomic segments.
Co-Author(s)
Rute Maria Pinto1, Will Harvey1, Jessica L. Quantrill3, Jiayun Yang2, Hui Min Lee1, Lu Lu1, Lonneke Vervelde1, Joe James4, Ashley Banyard4, Ian H. Brown4, Munir Iqbal2, Samantha Lycett1, Thomas P. Peacock2,3, Wendy Barclay3, Paul Digard1
1. The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, UK
2. The Pirbright Institute, Pirbright, Surrey, UK
3. Department of Infectious Diseases, Imperial College London, W2 1PG, UK
4. Department of Virology, Animal and Plant Health Agency (APHA-Weybridge), UK
Abstract Category
Transmission pathways, pathobiology, immune responses