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Influenza A(H7N9) V...
Influenza A(H7N9) Virus Acquires Resistance-Related Neuraminidase I222T Substitution When Infected Mallards Are Exposed to Low Levels of Oseltamivir in Water
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- Gillman, Anna (author)
- Uppsala universitet,Infektionssjukdomar
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- Nykvist, Marie (author)
- Uppsala universitet,Infektionssjukdomar,Institutionen för medicinsk biokemi och mikrobiologi
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- Muradrasoli, Shaman (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Inst för biomedicin och veterinär folkhälsovetenskap,Department of Biomedical Science and Veterinary Public Health
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- Söderström, Hanna (author)
- Umeå universitet,Kemiska institutionen,Umeå University
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- Wille, Michelle (author)
- Linnéuniversitetet,Institutionen för biologi och miljö (BOM),Ctr Ecol & Evolut Microbial Model Syst EEMiS
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- Daggfeldt, Annika (author)
- National Veterinary Institute
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- Bröjer, Caroline (author)
- National Veterinary Institute,National Veterinary Institute (SVA)
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- Waldenström, Jonas (author)
- Linnéuniversitetet,Institutionen för biologi och miljö (BOM),Ctr Ecol & Evolut Microbial Model Syst EEMiS
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- Olsen, Björn (author)
- Uppsala universitet,Infektionssjukdomar,Institutionen för medicinsk biokemi och mikrobiologi
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- Järhult, Josef D (author)
- Uppsala universitet,Infektionssjukdomar,Institutionen för medicinsk biokemi och mikrobiologi
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(creator_code:org_t)
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- American Society for Biochemistry and Molecular Biology, 2015
- 2015
- English.
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In: Antimicrobial Agents and Chemotherapy. - : American Society for Biochemistry and Molecular Biology. - 0066-4804 .- 1098-6596. ; 59:9, s. 5196-5202
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Abstract
Subject headings
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- Influenza A virus (IAV) has its natural reservoir in wild waterfowl, and new human IAVs often contain gene segments originating from avian IAVs. Treatment options for severe human influenza are principally restricted to neuraminidase inhibitors (NAIs), among which oseltamivir is stockpiled in preparedness for influenza pandemics. There is evolutionary pressure in the environment for resistance development to oseltamivir in avian IAVs, as the active metabolite oseltamivir carboxylate (OC) passes largely undegraded through sewage treatment to river water where waterfowl reside. In an in vivo mallard (Anas platyrhynchos) model, we tested if low-pathogenic avian influenza A(H7N9) virus might become resistant if the host was exposed to low levels of OC. Ducks were experimentally infected, and OC was added to their water, after which infection and transmission were maintained by successive introductions of uninfected birds. Daily fecal samples were tested for IAV excretion, genotype, and phenotype. Following mallard exposure to 2.5 mu g/liter OC, the resistance-related neuraminidase (NA) I222T substitution, was detected within 2 days during the first passage and was found in all viruses sequenced from subsequently introduced ducks. The substitution generated 8-fold and 2.4-fold increases in the 50% inhibitory concentration (IC50) for OC (P < 0.001) and zanamivir (P = 0.016), respectively. We conclude that OC exposure of IAV hosts, in the same concentration magnitude as found in the environment, may result in amino acid substitutions, leading to changed antiviral sensitivity in an IAV subtype that can be highly pathogenic to humans. Prudent use of oseltamivir and resistance surveillance of IAVs in wild birds are warranted.
Subject headings
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- Zoonotisk ekologi
- Zoonotic Ecology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Gillman, Anna
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Nykvist, Marie
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Muradrasoli, Sha ...
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Söderström, Hann ...
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Wille, Michelle
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Daggfeldt, Annik ...
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Bröjer, Caroline
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Waldenström, Jon ...
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Olsen, Björn
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Järhult, Josef D
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Microbiology
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Chemical Science ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Infectious Medic ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Microbiology in ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
- Articles in the publication
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Antimicrobial Ag ...
- By the university
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Linnaeus University
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Umeå University
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Uppsala University
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Swedish University of Agricultural Sciences