Conserved Expression and Functionality of Furin between Chickens and Ducks as an Activating Protease of Highly Pathogenic Avian Influenza Virus Hemagglutinins

Bruin, Anja C. M. de; Spronken, Monique I.; Bestebroer, Theo M.; Fouchier, Ron A. M.; Richard, Mathilde

doi:10.1128/spectrum.04602-22

Cited by 4 publications

(4 citation statements)

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“…The predominant proteases present in other cell types and how they may differ in distribution in turkeys compared to chickens, along with which proteases may differentially cleave the HA of the wt and ty-ad viruses, remain to be identified. However, conserved expression and functionality of furin protease has been observed between chickens and ducks [37]. Therefore, considering that turkeys and chickens are closely related, with ~90% genome identity [38], it is unlikely that separate protease compositions exist between the two species.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Evaluating the epizootic and zoonotic threat of an H7N9 low pathogenicity avian influenza virus (LPAIV) variant associated with enhanced pathogenicity in turkeys

James,

Thomas,

Seekings

et al. 2024

Preprint

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Between 2013-2017, A/Anhui/1/13-lineage H7N9 low pathogenicity avian influenza virus (LPAIV) was epizootic in chickens in China causing mild disease, with 616 fatal human cases. Despite poultry vaccination, H7N9 has not been eradicated. Previously we demonstrated increased pathogenesis in turkeys infected with H7N9, correlating with the emergence of the L217Q (L226Q H3 numbering) polymorphism in the haemagglutinin (HA) protein. A Q217 containing virus also arose and is now dominant in China following vaccination. Here, we compared infection and transmission of this Q217 containing turkey-adapted (ty-ad) isolate alongside the H7N9 (L217) wild-type (wt) virus in different poultry species and investigated the zoonotic potential in the ferret model. Both wt and ty-ad viruses demonstrated similar shedding and transmission in turkeys and chickens. However, the ty-ad virus was significantly more pathogenic than the wt virus in turkeys, causing 86% mortality in turkeys, but none in chickens. Expanded tissue tropism was seen for the ty-ad virus in turkeys but not chickens, yet the viral cell receptor distribution was broadly similar in visceral organs of both species. The ty-ad virus required exogenous trypsin for in vitro replication yet had increased replication in primary avian cells. Replication was comparable in mammalian cells and the ty-ad virus replicated successfully in ferrets. The L217Q polymorphism also affected HA antigenicity. Therefore, H7N9 infection in turkeys can generate novel variants with increased risk through altered pathogenicity and potential HA antigenic escape. These findings emphasise the requirement for enhanced surveillance and understanding of A/Anhui/1/13-lineage H7N9 viruses and their risk to different species.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluating the epizootic and zoonotic threat of an H7N9 low pathogenicity avian influenza virus (LPAIV) variant associated with enhanced pathogenicity in turkeys

James,

Thomas,

Seekings

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…The predominant proteases present in other cell types and how they may differ in distribution in turkeys compared to chickens, along with which proteases may differentially cleave the HA of the wt and ty-ad viruses, remain to be identified. However, conserved expression and functionality of the furin protease have been observed between chickens and ducks [42]. Therefore, considering that turkeys and chickens are closely related galliformes, with ~90% genome identity [43], it is unlikely that notably separate protease compositions exist between the two species.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the epizootic and zoonotic threat of an H7N9 low-pathogenicity avian influenza virus (LPAIV) variant associated with enhanced pathogenicity in turkeys

James,

Thomas,

Seekings

et al. 2024

Journal of General Virology

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Between 2013 and 2017, the A/Anhui/1/13-lineage (H7N9) low-pathogenicity avian influenza virus (LPAIV) was epizootic in chickens in China, causing mild disease, with 616 fatal human cases. Despite poultry vaccination, H7N9 has not been eradicated. Previously, we demonstrated increased pathogenesis in turkeys infected with H7N9, correlating with the emergence of the L217Q (L226Q H3 numbering) polymorphism in the haemagglutinin (HA) protein. A Q217-containing virus also arose and is now dominant in China following vaccination. We compared infection and transmission of this Q217-containing ‘turkey-adapted’ (ty-ad) isolate alongside the H7N9 (L217) wild-type (wt) virus in different poultry species and investigated the zoonotic potential in the ferret model. Both wt and ty-ad viruses demonstrated similar shedding and transmission in turkeys and chickens. However, the ty-ad virus was significantly more pathogenic than the wt virus in turkeys but not in chickens, causing 100 and 33% mortality in turkeys respectively. Expanded tissue tropism was seen for the ty-ad virus in turkeys but not in chickens, yet the viral cell receptor distribution was broadly similar in the visceral organs of both species. The ty-ad virus required exogenous trypsin for in vitro replication yet had increased replication in primary avian cells. Replication was comparable in mammalian cells, and the ty-ad virus replicated successfully in ferrets. The L217Q polymorphism also affected antigenicity. Therefore, H7N9 infection in turkeys can generate novel variants with increased risk through altered pathogenicity and potential HA antigenic escape. These findings emphasize the requirement for enhanced surveillance and understanding of A/Anhui/1/13-lineage viruses and their risk to different species.

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“…The evolution of LPAI-to-HPAI in both H5 and H7 influenza virus subtypes is the result of a genetic predisposition that allows the gain of multiple basic amino acids at the cleavage site of the immature HA gene ( 5 ). As a result, the HA undergoes activation by cellular endoproteases that exist in cells through multiple avian and organ tissues allowing efficient replication of the virus in several organs resulting in a severe systemic disease ( 6 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

Sequence-based epitope mapping of high pathogenicity avian influenza H5 clade 2.3.4.4b in Latin America

Ospina-Jimenez,

Gomez,

Osorio-Zambrano

et al. 2024

Front. Vet. Sci.

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High Pathogenicity Avian Influenza (HPAI) poses a significant threat to public and animal health. Clade 2.3.4.4b recently emerged from the Eastern hemisphere and disseminated globally, reaching the Latin American (LATAM) region in late 2022 for the first time. HPAI in LATAM has resulted in massive mortalities and culling of poultry and wild birds, causing infection in mammals and humans. Despite its meaningful impact in the region, only occasional evidence about the genetic and epitope characteristics of the introduced HPAI is reported. Hence, this study seeks to phylogenetically characterize the molecular features and the source of HPAI in LATAM by evaluating potential antigenic variations. For such a purpose, we analyzed 302 whole genome sequences. All Latin American viruses are descendants of the 2.3.4.4b clade of the European H5N1 subtype. According to genomic constellations deriving from European and American reassortments, the identification of three major subtypes and eight sub-genotypes was achievable. Based on the variation of antigenic motifs at the HA protein in LATAM, we detected three potential antigenic variants, indicating the HA-C group as the dominant variant. This study decidedly contributes to unraveling the origin of the 2.3.4.4b clade in LATAM, its geographic dissemination, and evolutionary dynamics within Latin American countries. These findings offer useful information for public health interventions and surveillance initiatives planned to prevent and manage the transmission of avian influenza viruses.

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Conserved Expression and Functionality of Furin between Chickens and Ducks as an Activating Protease of Highly Pathogenic Avian Influenza Virus Hemagglutinins

Abstract: HPAIV outbreaks are a global concern due to the health risks for poultry, wildlife, and humans and their major economic impact. The number of LPAIV-to-HPAIV conversions, which is associated with spillover from wild birds to poultry, has been increasing over recent decades.

Cited by 4 publications

References 71 publications

Evaluating the epizootic and zoonotic threat of an H7N9 low pathogenicity avian influenza virus (LPAIV) variant associated with enhanced pathogenicity in turkeys

Evaluating the epizootic and zoonotic threat of an H7N9 low pathogenicity avian influenza virus (LPAIV) variant associated with enhanced pathogenicity in turkeys

Evaluating the epizootic and zoonotic threat of an H7N9 low-pathogenicity avian influenza virus (LPAIV) variant associated with enhanced pathogenicity in turkeys

Sequence-based epitope mapping of high pathogenicity avian influenza H5 clade 2.3.4.4b in Latin America

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