#17,929
The avian flu threat we were facing a decade ago (Feb 2014) was far different from what we see today. The HPAI H5 threat was still concentrated in Asia, the Middle East, and Western Africa - with the virus making only occasional, short-lived, forays into Europe.
Although we'd seen some evidence of long-distance carriage of HPAI viruses by migratory birds, their role in spreading the virus was still very much a matter of bitter debate (see Bird Flu Spread: The Flyway Or The Highway?).
While a newly emerging HPAI H5N8 would appear in South Korean poultry in early 2014 with an improved ability to be carried by migratory birds (see J Vet Sci: Evolution, Global Spread, And Pathogenicity Of HPAI H5Nx Clade 2.3.4.4), LPAI H5 and H7 viruses have another parlor trick; the ability to spontaneous mutate into an HPAI strain.
Now that HPAI viruses like H5N1 are more easily winging their way around the globe in migratory birds, that may seem less important, but this remains a credible route for seeing new HPAI H5 and H7 viruses emerge.
Our understanding of how this happens is limited, and is based primarily on observations from a few dozen documented incidents in poultry, but it prompted the OIE (now WOAH) to make LPAI H5 and H7 viruses reportable in 2006, and infected captive birds subject to immediate eradication (see Terrestrial Animal Code Article 10.4.1.).
HPAI viruses have been generated in the lab by repeated passage of LPAI viruses through chickens (cite FAO) but exactly how and why this occurs naturally is poorly understood (see JVI Emergence of a Highly Pathogenic Avian Influenza Virus from a Low Pathogenic Progenitor).
All of which brings us to a new research article in PLoS Pathogens which describes experiments where both poultry and wild ducks were inoculated with LPAI and HPAI H7N7 viruses, and the resultant spread and/or mutation of these viruses.
This is a lengthy, and at times highly technical report, that seems to bear out the theory that spontaneous LPAI-to-HPAI mutations are far more likely to occur in poultry than in wild ducks. Furthermore, HPAI H7N7 viruses had difficulty competing with LPAI strains in wild ducks.
Due to its length, I've only posted the link, Abstract, and Author's summary. I'll have a bit more after the break.
Anja C. M. de Bruin, Monique I. Spronken, Adinda Kok, Miruna E. Rosu, Dennis de Meulder,Stefan van Nieuwkoop, Pascal Lexmond, Mathis Funk, Lonneke M. Leijten, Theo M. Bestebroer, Sander Herfst, Debby van Riel,Ron A. M. Fouchier,Mathilde Richard
Published: February 26, 2024
https://doi.org/10.1371/journal.ppat.1011942
Abstract
Highly pathogenic avian influenza viruses (HPAIVs) cause severe hemorrhagic disease in terrestrial poultry and are a threat to the poultry industry, wild life, and human health. HPAIVs arise from low pathogenic avian influenza viruses (LPAIVs), which circulate in wild aquatic birds. HPAIV emergence is thought to occur in poultry and not wild aquatic birds, but the reason for this species-restriction is not known.
We hypothesized that, due to species-specific tropism and replication, intrahost HPAIV selection is favored in poultry and disfavored in wild aquatic birds. We tested this hypothesis by co-inoculating chickens, representative of poultry, and ducks, representative of wild aquatic birds, with a mixture of H7N7 HPAIV and LPAIV, mimicking HPAIV emergence in an experimental setting. Virus selection was monitored in swabs and tissues by RT-qPCR and immunostaining of differential N-terminal epitope tags that were added to the hemagglutinin protein.
HPAIV was selected in four of six co-inoculated chickens, whereas LPAIV remained the major population in co-inoculated ducks on the long-term, despite detection of infectious HPAIV in tissues at early time points. Collectively, our data support the hypothesis that HPAIVs are more likely to be selected at the intrahost level in poultry than in wild aquatic birds and point towards species-specific differences in HPAIV and LPAIV tropism and replication levels as possible explanations.
Author summary
Highly pathogenic avian influenza viruses (HPAIVs) cause severe disease in poultry with mortality rates reaching 100% and, therefore, pose a large burden on the poultry industry. Additionally, some HPAIVs have spilled back from poultry into wild bird populations, increasing their geographic spread. HPAIVs arise from low pathogenic avian influenza viruses (LPAIVs), which circulate in wild aquatic birds and occasionally spillover into poultry.
LPAIV to HPAIV conversion is associated with terrestrial poultry species, but the reasons underlying this species-restriction are unknown. The second step of HPAIV emergence, following HPAIV genesis, constitutes of the intrahost selection of the HPAIV from the large pool of replicating LPAIVs. Here, we investigated whether the intrahost selection efficiency differs between chickens and ducks, models for poultry and wild aquatic birds respectively, by co-inoculating them with HPAIV and LPAIV. Tagged viruses were utilized to monitor LPAIV and HPAIV frequencies at both the RNA and protein level. The HPAIV was selected in a majority of the chickens, demonstrated by the development of canonical HPAI disease and infectious HPAIV shedding, whereas all ducks solely shed infectious LPAIV. These results confirm that intrahost selection of HPAIVs is species-specific, which likely contributes to the restriction of HPAIV-emergence to poultry populations.
It is possible that the use of a different subtype (i.e. newer HPAI H5 viruses), or a broader range of avian hosts, might return somewhat different results.
Carriage of HPAI H5 viruses by aquatic birds was generally short-lived, restricting its spread.
