(INF-P7) Oseltamivir-resistant avian H1N1 influenza A virus can transmit from mallards to chickens

Författare/Medförfattare

NamnArbetsplatsOrganisationOrtLandAffiliation
Erik Skog Infektionskliniken, Akademiska sjukhuset Institutionen för medicinska vetenskaper, Uppsala Universitet Uppsala 1
Marie Nykvist Zoonosis Science Center Institutionen för medicinsk biokemi och mikrobiologi, Uppsala Universitet Uppsala 2
Michelle Wille Zoonosis Science Center Institutionen för medicinsk biokemi och mikrobiologi, Uppsala Universitet Uppsala 2
Mahmoud M Naguib Zoonosis Science Center Institutionen för medicinsk biokemi och mikrobiologi, Uppsala Universitet Uppsala 2
Josef D Järhult Infektionskliniken, Akademiska sjukhuset Institutionen för medicinska vetenskaper, Uppsala Universitet Uppsala 2

Abstrakt

Oseltamivir is stockpiled globally as influenza pandemic preparedness. Thus, a pandemic influenza virus resistant to oseltamivir would potentially lead to a public health disaster. The active metabolite oseltamivir carboxylate (OC) is stable and has been found in river water where mallards, the natural host of influenza virus, can be exposed. We have previously shown OC resistance in avian influenza infected mallards exposed to environmental-like OC concentrations. The resistance mutation NA-H274Y persisted in a H1N1 virus without drug pressure suggesting maintained fitness.

Poultry is an intermediate host between mallards and humans. In our first study we investigated if resistant avian H1N1 (H1N1/H274Y) could transmit from mallards to chickens and in between chickens in an in vivo model. Mallards where infected oesophageally with H1N1/H274Y and H1N1wt, respectively. Generations of mallards and chickens were successively introduced. Daily fecal samples were subjected to a real-time RT-PCR. For positive samples the neuraminidase gene was Sanger sequenced. In the second study chickens were infected oculo-nasally with H1N1/H274Y and H1N1wt respectively before another generation was introduced. Fecal and oropharyngeal samples were taken daily.

In the first study H1N1/H274Y was found in fecal samples from one chicken of the first generation four days in a row. In the H1N1wt experiment one chicken of the first generation had positive fecal samples three days in a row. In the second study four chickens infected with H1N1/H274Y and one with H1N1wt had positive oropharyngeal samples 2-4 days in a row. No fecal samples were positive.

Our results demonstrate that an oseltamivir-resistant avian influenza virus can transmit from mallards and replicate in chickens. The resistance mutation NA-H274Y does not constitute a barrier to interspecies transmission per se, as the mutant virus did not perform inferior to the wild-type counterpart. However, none of the viruses established a sustained transmission in chickens.