[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]
J Virol 2020 Jan 22 [Online ahead of print]
Emergence and Selection of a Highly Pathogenic Avian Influenza H7N3 Virus
Nancy Beerens 1, Rene Heutink 2, Frank Harders 2, Alex Bossers 2, Guus Koch 2, Ben Peeters 2
Affiliations: 1 Wageningen Bioveterinary Research, Lelystad, The Netherlands. nancy.beerens@wur.nl. 2 Wageningen Bioveterinary Research, Lelystad, The Netherlands.
PMID: 31969434 DOI: 10.1128/JVI.01818-19
Abstract
Low pathogenic avian influenza (LPAI) viruses of subtypes H5 and H7 have the ability to spontaneously mutate to highly pathogenic (HPAI) variants, causing high mortality in poultry. The highly pathogenic phenotype is caused by mutation of the hemagglutinin (HA) cleavage site, but additional mutations may play a role. Evidence from the field for the switch to high pathogenicity remains scarce. This study provides direct evidence for LPAI to HPAI mutation during H7N3 infection of a turkey farm in the Netherlands. No severe clinical symptoms were reported at the farm, but deep-sequencing revealed a minority of HPAI sequences (0.06%) in the virus population isolated from infected turkeys. The HPAI virus contained a 12-nucleotide insertion in the HA cleavage site, that was likely introduced by a single event, as no intermediates with shorter inserts were identified. This suggests non-homologous recombination as the mechanism of insertion. Analysis of different organs of the infected turkeys showed the highest amount of HPAI virus in the lung (4.4%). The HPAI virus was rapidly selected in experimentally infected chickens, after both intravenous and intranasal/intratracheal inoculation with the mixed virus preparation. Full-genome sequencing revealed that both pathotypes contained a deletion in the stalk region of the neuraminidase protein. We identified additional mutations in HA and polymerase basic protein 1 (PB1) in the HPAI virus, which were already present as minority variants in the LPAI virus population. Our findings provide more insight in the molecular changes and mechanisms involved in the emergence and selection of HPAI viruses.
IMPORTANCE
Low pathogenic avian influenza (LPAI) viruses circulate in wild birds, and can be transmitted to poultry. LPAI viruses can mutate to become highly pathogenic avian influenza (HPAI) viruses causing severe disease and death in poultry. Little is known about this switch to high pathogenicity. We isolated a LPAI H7N3 virus from an infected turkey farm, and showed that this contains small amounts of HPAI virus. The HPAI virus rapidly outcompeted the LPAI virus in chickens that were experimentally infected with this mixture of viruses. We analysed the genome sequences of the LPAI and HPAI viruses, and identified several changes that may be important for a virus to become highly pathogenic. This knowledge may be used for timely identification of LPAI viruses that pose a risk of becoming highly pathogenic in the field.
Copyright © 2020 American Society for Microbiology.
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Keywords: Avian Influenza; H7N3; Poultry; Netherlands.
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