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Environmental levels of the antiviral oseltamivir induce development of resistance mutation H274Y in influenza A/H1N1 virus in mallards
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- Järhult, Josef D. (author)
- Uppsala universitet,Infektionssjukdomar,Department of Medical Sciences,Institutionen för medicinska vetenskaper
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- Muradrasoli, Shaman (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Inst för biomedicin och veterinär folkhälsovetenskap,Department of Biomedical Science and Veterinary Public Health,Section of Bacteriology and Food Safety, Department of,Section of Bacteriology and Food Safety, Department of
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- Wahlgren, John (author)
- Swedish Institute for Infectious Disease Control ; Karolinska Institutet,Swedish Institute for Infectious Disease Control,Karolinska Institutet
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- Söderström, Hanna (author)
- Umeå universitet,Kemiska institutionen,Umeå University
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- Orozovic, Goran (author)
- Linnéuniversitetet,Institutionen för naturvetenskap, NV,Faculty of Health and Life Sciences,Fakulteten för Hälso- och livsvetenskap
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- Gunnarsson, Gunnar (author)
- Linnéuniversitetet,Institutionen för naturvetenskap, NV,Kristianstad University,Akvatisk biologi och kemi
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- Bröjer, Caroline (author)
- National Veterinary Institute ; Swedish University of Agricultural Sciences,National Veterinary Institute, Uppsala,National Veterinary Institute, Uppsala
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- Latorre-Margalef, Neus (author)
- Linnéuniversitetet,Institutionen för naturvetenskap, NV,Faculty of Health and Life Sciences,Fakulteten för Hälso- och livsvetenskap
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- Fick, Jerker (author)
- Umeå universitet,Kemiska institutionen,Umeå University
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- Grabic, Roman (author)
- Umeå universitet,Kemiska institutionen,Umeå University ; University of South Bohemia in Ceske Budejovice, Czech Republic,Umeå University
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- Lennerstrand, Johan (author)
- Uppsala universitet,Klinisk virologi,Department of Medical Sciences,Institutionen för medicinska vetenskaper
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- Waldenström, Jonas (author)
- Linnéuniversitetet,Institutionen för naturvetenskap, NV,Zoonotic Ecology and Epidemiology,Faculty of Health and Life Sciences,Fakulteten för Hälso- och livsvetenskap
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- Lundkvist, Ake (author)
- Karolinska Institutet,Swedish Institute for Infectious Disease Control
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- Olsen, Björn (author)
- Uppsala universitet,Linnéuniversitetet,Institutionen för naturvetenskap, NV,Uppsala University,Infektionssjukdomar,Department of Medical Sciences,Institutionen för medicinska vetenskaper
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(creator_code:org_t)
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- 2011-09-12
- 2011
- English.
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In: PLOS ONE. - San Francisco, CA : Public Library of Science (PLoS). - 1932-6203. ; 6:9
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Abstract
Subject headings
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- Oseltamivir (Tamiflu®) is the most widely used drug against influenza infections and is extensively stockpiled worldwide as part of pandemic preparedness plans. However, resistance is a growing problem and in 2008-2009, seasonal human influenza A/H1N1 virus strains in most parts of the world carried the mutation H274Y in the neuraminidase gene which causes resistance to the drug. The active metabolite of oseltamivir, oseltamivir carboxylate (OC), is poorly degraded in sewage treatment plants and surface water and has been detected in aquatic environments where the natural influenza reservoir, dabbling ducks, can be exposed to the substance. To assess if resistance can develop under these circumstances, we infected mallards with influenza A/H1N1 virus and exposed the birds to 80 ng/L, 1 µg/L and 80 µg/L of OC through their sole water source. By sequencing the neuraminidase gene from fecal samples, we found that H274Y occurred at 1 µg/L of OC and rapidly dominated the viral population at 80 µg/L. IC₅₀ for OC was increased from 2-4 nM in wild-type viruses to 400-700 nM in H274Y mutants as measured by a neuraminidase inhibition assay. This is consistent with the decrease in sensitivity to OC that has been noted among human clinical isolates carrying H274Y. Environmental OC levels have been measured to 58-293 ng/L during seasonal outbreaks and are expected to reach µg/L-levels during pandemics. Thus, resistance could be induced in influenza viruses circulating among wild ducks. As influenza viruses can cross species barriers, oseltamivir resistance could spread to human-adapted strains with pandemic potential disabling oseltamivir, a cornerstone in pandemic preparedness planning. We propose surveillance in wild birds as a measure to understand the resistance situation in nature and to monitor it over time. Strategies to lower environmental levels of OC include improved sewage treatment and, more importantly, a prudent use of antivirals.
Subject headings
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Ekologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Ecology (hsv//eng)
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- LANTBRUKSVETENSKAPER -- Husdjursvetenskap (hsv//swe)
- AGRICULTURAL SCIENCES -- Animal and Dairy Sience (hsv//eng)
- LANTBRUKSVETENSKAPER -- Veterinärmedicin (hsv//swe)
- AGRICULTURAL SCIENCES -- Veterinary Science (hsv//eng)
Keyword
- a virus
- neuraminidase
- europe
- ducks
- Zoonotic Ecology
- Zoonotisk ekologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Järhult, Josef D ...
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Muradrasoli, Sha ...
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Wahlgren, John
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Söderström, Hann ...
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Orozovic, Goran
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Gunnarsson, Gunn ...
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show more...
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Bröjer, Caroline
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Latorre-Margalef ...
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Fick, Jerker
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Grabic, Roman
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Lennerstrand, Jo ...
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Waldenström, Jon ...
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Lundkvist, Ake
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Olsen, Björn
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show less...
- 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 Biological Scien ...
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and Ecology
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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- AGRICULTURAL SCIENCES
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AGRICULTURAL SCI ...
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and Animal and Dairy ...
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- AGRICULTURAL SCIENCES
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AGRICULTURAL SCI ...
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and Veterinary Scien ...
- Articles in the publication
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PLOS ONE
- By the university
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Linnaeus University
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Umeå University
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Karolinska Institutet
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Swedish University of Agricultural Sciences
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Uppsala University
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Kristianstad University College