Influenza A/H4N2 mallard infection experiments further indicate zanamivir as less prone to induce environmental resistance development than oseltamivir

Tepper, Viktoria; Nykvist, Marie; Gillman, Anna; Skog, E; Wille, Michelle; Lindström, Hanna; Tang, Chaojun; Lindberg, Richard H.; Lundkvist, Åke; Järhult, Josef D.

doi:10.1099/jgv.0.001369

Cited by 6 publications

(4 citation statements)

References 36 publications

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“…Following oesophageal inoculation, all mallards were infected starting at 1 day p.i. and followed similar shedding pattern as seen in previous experiments using the same bird model [29–32, 34, 35]. These experimentally infected mallards successfully infected the contact mallards (gen. 2) ( in Methods).…”

Section: Resultssupporting

confidence: 79%

“…AIVs replicating in the intestines of wild waterfowl can thus get exposed to OC allowing for resistance development. Several in vivo studies exposing AIV-infected mallards to NAIs in experimental settings mimicking the natural exposure, support the occurrence of resistance development via this route [29–33]. For example, a low pathogenic AIV H1N1 strain developed oseltamivir resistance through the NA-H274Y (N2 numbering) amino acid substitution in the neuraminidase (NA) gene when exposed to 950 ng l –1 OC (the same magnitude as found in river water) in the water source of the mallards [34].…”

Section: Introductionmentioning

confidence: 99%

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An oseltamivir-resistant avian H1N1 influenza A virus can transmit from mallards to chickens similarly to a wild-type strain: implications for the risk of resistance transmission to humans

Skog

Nykvist

Naguib

et al. 2023

Journal of General Virology

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The neuraminidase inhibitor (NAI) oseltamivir is stockpiled globally as part of influenza pandemic preparedness. However, oseltamivir carboxylate (OC) resistance develops in avian influenza virus (AIV) infecting mallards exposed to environmental-like OC concentrations, suggesting that environmental resistance is a real concern. Herein we used an in vivo model to investigate if avian influenza H1N1 with the OC-resistant mutation NA-H274Y (51833/H274Y) as compared to the wild-type (wt) strain (51833 /wt) could transmit from mallards, which would potentially be exposed to environmentally contaminated environments, to and between chickens, thus posing a potential zoonotic risk of antiviral-resistant AIV. Regardless of whether the virus had the OC-resistant mutation or not, chickens became infected both through experimental infection, and following exposure to infected mallards. We found similar infection patterns between 51833/wt and 51833/H274Y such that, one chicken inoculated with 51833/wt and three chickens inoculated with 51833/H274Y were AIV positive in oropharyngeal samples more than 2 days consecutively, indicating true infection, and one contact chicken exposed to infected mallards was AIV positive in faecal samples for 3 consecutive days (51833/wt) and another contact chicken for 4 consecutive days (51833/H274Y). Importantly, all positive samples from chickens infected with 51833/H274Y retained the NA-H274Y mutation. However, none of the virus strains established sustained transmission in chickens, likely due to insufficient adaptation to the chicken host. Our results demonstrate that an OC-resistant avian influenza virus can transmit from mallards and replicate in chickens. NA-H274Y does not constitute a barrier to interspecies transmission per se, as the resistant virus did not show reduced replicative capacity compared to the wild-type counterpart. Thus, responsible use of oseltamivir and surveillance for resistance development is warranted to limit the risk of an OC-resistant pandemic strain.

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Section: Resultssupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

An oseltamivir-resistant avian H1N1 influenza A virus can transmit from mallards to chickens similarly to a wild-type strain: implications for the risk of resistance transmission to humans

Skog

Nykvist

Naguib

et al. 2023

Journal of General Virology

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“…However, we did not find any change at these 2 sites in all H4N2 viruses, indicating that they retained the avian-like receptor-binding preference ( Naeve et al, 1984 ; Matrosovich et al, 2000 ). The absence of E119G and H274N mutations on NA indicated that there were no neuraminidase inhibitors ( NAIs ) resistance mutations ( Tepper et al, 2020 ). No amino acid deletions were observed in the NA stalk region.…”

Section: Resultsmentioning

confidence: 99%

Characterization of avian influenza A (H4N2) viruses isolated from wild birds in Shanghai during 2019 to 2021

Tang²,

Gu³

et al. 2023

Poultry Science

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“…fish, daphnids and others (ChV). In compliance with the benchmarking criteria all the intermediates were characterized with a log Kow of ≤ 5 and, a BCF value of < 5000 L/kg, suggesting that these TPs did not exhibit the risk of bioaccumulation and associated biomagnification ( Tepper et al, 2020 ). Also, according to the PBT criteria proposed by US-EPA and the European Commission (EC), none of the produced TPs exhibited long-range transport potential in water bodies ( Table S5 ).…”

Section: Quantitative Analysis With Eps-subtypes and Secondary Structure Proteinsmentioning

confidence: 89%

Unravelling multiple removal pathways of oseltamivir in wastewater by microalgae through experimentation and computation

Zeeshan

Qiu

et al. 2022

Journal of Hazardous Materials

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Increased worldwide consumption of antiviral drugs (AVDs) amid COVID-19 has induced enormous burdens to the existing wastewater treatment systems. Microalgae-based bioremediation is a competitive alternative technology due to its simultaneous nutrient recovery and sustainable biomass production. However, knowledge about the fate, distribution, and interaction of AVDs with microalgae is yet to be determined. In this study, a concentration-determined influence of AVD oseltamivir (OT) was observed on the biochemical pathway of Chlorella sorkiniana (C.S-N1) in synthetic municipal wastewater. The results showed that high OT concentration inhibited the biomass growth through increased oxidative stress, and restrained photosynthesis. Nevertheless, complete OT removal was achieved at its optimized concentration of 10 mg/L by various biotic (82%) and abiotic processes (18.0%). The chemical alterations in three subtypes of extracellular polymeric substances (EPS) were primarily investigated by electrostatic (OT +8.22 mV vs. C.S-N1 -18.31 mV) and hydrophobic interactions between EPS-OT complexes supported by secondary structure protein analysis. Besides, six biodegradation-catalyzed transformation products were identified by quadrupole-time-of-flight mass spectrometer and by density functional theory. Moreover, all the TPs exhibited log Kow ≤ 5 and bioconcentration factor values of < 5000 L/kg, meeting the practical demands of environmental sustainability. This study broadens our understanding of microalgal bioadsorption and biodegradation, promoting microalgae bioremediation for nutrient recovery and AVDs removal.

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Influenza A/H4N2 mallard infection experiments further indicate zanamivir as less prone to induce environmental resistance development than oseltamivir

Abstract: World HealtH orgaNizatioN geneva orgaNiSatioN moNdiale de la SaNté genève annual subscription / abonnement annuel sw. fr. / Fr. s. 346.-

Cited by 6 publications

References 36 publications

An oseltamivir-resistant avian H1N1 influenza A virus can transmit from mallards to chickens similarly to a wild-type strain: implications for the risk of resistance transmission to humans

An oseltamivir-resistant avian H1N1 influenza A virus can transmit from mallards to chickens similarly to a wild-type strain: implications for the risk of resistance transmission to humans

Characterization of avian influenza A (H4N2) viruses isolated from wild birds in Shanghai during 2019 to 2021

Unravelling multiple removal pathways of oseltamivir in wastewater by microalgae through experimentation and computation

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