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Seekings, A. H.

Publications and source records attributed to Seekings, A. H..

3 recordsLinked to original sources

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

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. 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 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 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 viruses and their risk to different species.

microbiology↗

Transmission dynamics and pathogenesis differ between pheasants and partridges infected with clade 2.3.4.4b H5N8 and H5N1 high-pathogenicity avian influenza viruses

During the UK 2020-2021 epizootic of H5Nx clade 2.3.4.4b high-pathogenicity avian influenza viruses (HPAIVs), high mortality occurred during incursions in commercially farmed common pheasants (Phasianus colchicus). Two pheasant farms, affected separately by H5N8 and H5N1 subtypes, included adjacently housed red-legged partridges (Alectoris rufa), which appeared to be unaffected. Despite extensive ongoing epizootics, H5Nx HPAIV partridge outbreaks were not reported during 2020-2021 and 2021-2022 in the UK, so it is postulated that partridges are more resistant to HPAIV infection than other gamebirds. To assess this, pathogenesis and both intra- and inter-species transmission of UK pheasant-origin H5N8-2021 and H5N1-2021 HPAIVs were investigated. Onward transmission to chickens was also assessed to better understand the risk of spread from gamebirds to other commercial poultry sectors. A lower infectious dose was required to infect pheasants with H5N8-2021 compared to H5N1-2021. However, HPAIV systemic dissemination to multiple organs within pheasants was more rapid following infection with H5N1-2021 than H5N8-2021, with the former attaining generally higher viral RNA levels in tissues. Intraspecies transmission to contact pheasants was successful for both viruses and associated with viral environmental contamination, while interspecies transmission to a first chicken-contact group was also efficient. However, further onward transmission to additional chicken contacts was only achieved with H5N1-2021. Intra-partridge transmission was only successful when high-dose H5N1-2021 was administered, while partridges inoculated with H5N8-2021 failed to shed and transmit, although extensive tissue tropism was observed for both viruses. Mortalities among infected partridges featured a longer incubation period compared to that in pheasants, for both viruses. Therefore, the susceptibility of different gamebird species and pathogenicity outcomes to the ongoing H5Nx clade 2.3.4.4b HPAIVs varies, but pheasants represent a greater likelihood of H5Nx HPAIV introduction into galliforme poultry settings. Consequently, viral maintenance within gamebird populations and risks to poultry species warrant enhanced investigation.

microbiology↗

Investigating the genetic diversity of H5 avian influenza in the UK 2020-2022

Since 2020, the UK and Europe, have experienced annual epizootics of high pathogenicity avian influenza virus (HPAIV). The first during autumn/winter 2020/21 involved the detected with six H5Nx subtypes although H5N8 HPAIV dominated in the UK. Whilst genetic assessment of the H5N8 HPAIVs within the UK demonstrated relative homogeneity, there was a background of other genotypes circulating at a lower degree with different neuraminidase and internal genes. Following a small number of summer detections of H5N1 in wild birds over the summer of 2021, autumn/winter 2021/22 saw another European H5 HPAIV epizootic, that has dwarfed the prior epizootic. This second epizootic was dominated almost exclusively by H5N1 HPAIV, although six distinct genotypes were defined. We have used genetic analysis to evaluate the emergence of different genotypes and proposed reassortment events that have been observed. The existing data suggests that the H5N1 circulating in Europe during late 2020, continued to circulate in wild birds throughout 2021, with minimal adaptation, but has then gone on to reassort with AIVs in the wild bird population. We have undertaken an in-depth genetic assessment of H5 HPAIVs detected in the UK, over the last two winter seasons and demonstrate the utility of in-depth genetic analyses in defining the diversity of H5 HPAIVs circulating in avian species, the potential for zoonotic risk and whether incidents of lateral spread can be defined over independent incursion of infection from wild birds. Key supporting data for mitigation activities. ImportanceHigh pathogenicity avian influenza virus (HPAIV) outbreaks devastate avian species across all sectors having both economic and ecological impacts through mortalities in poultry and wild birds, respectively. These viruses can also represent a significant zoonotic risk. Since 2020, the UK has experienced two successive outbreaks of H5 HPAIV. Whilst H5N8 HPAIV was predominant during the 2020/21 outbreak, other H5 subtypes were also detected. The following year there was a shift in subtype dominance to H5N1 HPAIV, but multiple H5N1 genotypes were detected. Through thorough utilisation of whole-genome sequencing, it was possible to track and characterise the genetic evolution of these H5 HPAIVs in UK poultry and wild birds. This has enabled us to assess the risk posed by these viruses at the poultry:wild bird and the avian:human interface and to investigate potential lateral spread between infected premises, a key factor in understanding threat to the commercial sector.

molecular biology↗