Environmental levels of oseltamivir induce development of resistance mutation H274Y in influenza A/H1N1 virus in mallards – implications for the risk of an oseltamivir resistant influenza pandemic

• Resistance in influenza is a growing problem. Oseltamivir carboxylate (OC), the active substance of the most widely used antiviral drug oseltamivir (Tamiflu ®), is poorly degraded in sewage treatment plants and surface water. OC has been detected in aquatic environments where the natural influenza reservoir, dabbling ducks, can be exposed to it. To test if resistance can occur in this situation, we infected mallards with influenza A/H1N1 virus and exposed the birds to 0.08 μg /L, 1.00 μg/L and 80.00 μg/L of OC. The resistance mutation H274Y occurred at 1 μg/L and rapidly dominated the viral population at 80 μg/L. The environmental levels of OC are expected to reach this magnitude. IC50 for OC was increased from 1-4 nM to 400-700 nM in H274Y-positive isolates, confirming a resistant phenotype. As influenza viruses can cross the species barrier, resistance to oseltamivir can spread to human-adapted strains with pandemic potential disabling one of the cornerstones in pandemic preparedness planning.

Ämnesord

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)

Nyckelord

Virology

Virologi

Zoonotic Ecology

Zoonotisk ekologi

Publikations- och innehållstyp

vet (ämneskategori)

ovr (ämneskategori)