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Open AccessArticle

Insights into the Acquisition of Virulence of Avian Influenza Viruses during a Single Passage in Ferrets

1
The Commonwealth Scientific and Industrial Research Organisation, Australian Animal Health Laboratory (CSIRO-AAHL), Geelong 3219, Victoria, Australia
2
Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute of Infection and Immunity, Melbourne 3000, Victoria, Australia
3
Seqirus, 63 Poplar Rd, Parkville 3052, Victoria, Australia
*
Author to whom correspondence should be addressed.
Those authors contribute equally to this work.
Viruses 2019, 11(10), 915; https://doi.org/10.3390/v11100915
Received: 9 August 2019 / Revised: 6 September 2019 / Accepted: 10 September 2019 / Published: 4 October 2019
(This article belongs to the Section Animal Viruses)
Circulating avian influenza viruses pose a significant threat, with human infections occurring infrequently but with potentially severe consequences. To examine the dynamics and locale of the adaptation process of avian influenza viruses when introduced to a mammalian host, we infected ferrets with H5N1 viruses. As expected, all ferrets infected with the human H5N1 isolate A/Vietnam/1203/2004 showed severe disease and virus replication outside the respiratory tract in multiple organs including the brain. In contrast infection of ferrets with the avian H5N1 virus A/Chicken/Laos/Xaythiani26/2006 showed a different collective pattern of infection; many ferrets developed and cleared a mild respiratory infection but a subset (25–50%), showed extended replication in the upper respiratory tract and developed infection in distal sites. Virus from these severely infected ferrets was commonly found in tissues that included liver and small intestine. In most instances the virus had acquired the common virulence substitution PB2 E627K but, in one case, a previously unidentified combination of two amino acid substitutions at PB2 S489P and NP V408I, which enhanced polymerase activity, was found. We noted that virus with high pathogenicity adaptations could be dominant in an extra-respiratory site without being equally represented in the nasal wash. Further ferret passage of these mutated viruses resulted in high pathogenicity in all ferrets. These findings illustrate the remarkable ability of avian influenza viruses that avoid clearance in the respiratory tract, to mutate towards a high pathogenicity phenotype during just a single passage in ferrets and also indicate a window of less than 5 days in which treatment may curtail systemic infection.
Keywords: avian influenza; ferret; mammalian adaptation; H5N1 influenza virus; systemic infection avian influenza; ferret; mammalian adaptation; H5N1 influenza virus; systemic infection
MDPI and ACS Style

Butler, J.; Middleton, D.; Haining, J.; Layton, R.; Rockman, S.; Brown, L.E.; Sapats, S. Insights into the Acquisition of Virulence of Avian Influenza Viruses during a Single Passage in Ferrets. Viruses 2019, 11, 915.

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