The transmissibility of these viruses further highlights the pandemic potential of AIVs in the wild bird reservoir and the need to maintain surveillance.

Jude Childrens Research Hospital, Memphis, TN 38105; b Veterinary Pathology Core, St.

Jude Childrens Research Hospital, Memphis, TN 38105; Find this author on Google Scholar.

Jude Childrens Research Hospital, Memphis, TN 38105 Find this author on Google Scholar.

Webster, August 10, 2017 (sent for review March 14, 2017; reviewed by Wendy Barclay, Todd T.

Our study of a group of similar subtype H1N1 avian influenza viruses (AIVs) isolated at Delaware Bay, USA, revealed genetic markers for airborne transmission in nonstructural genes.

Viruses not containing all markers lacked airborne transmissibility in the ferret model.

We revealed a role for Nonstructural Protein 1 (NS1) in facilitating airborne transmission that was associated with viral replication in the upper respiratory tract (URT).

Nonairborne-transmissible NS1 mutants showed delayed viral maturation, resulting in limited tissue pathology and little virus at the mucosa.

Overall, our study has revealed insights into viral replication in the URT associated with the airborne transmissibility of AIVs in mammals.

Abstract North American wild birds are an important reservoir of influenza A viruses, yet the potential of viruses in this reservoir to transmit and cause disease in mammals is not well understood.

Our surveillance of avian influenza viruses (AIVs) at Delaware Bay, USA, revealed a group of similar H1N1 AIVs isolated in 2009, some of which were airborne-transmissible in the ferret model without prior adaptation.

Comparison of the genomes of these viruses revealed genetic markers of airborne transmissibility in the Polymerase Basic 2 (PB2), PB1, PB1-F2, Polymerase Acidic-X (PA-X), Nonstructural Protein 1 (NS1), and Nuclear Export Protein (NEP) genes.

Viral maturation was also delayed, evident as strong intranuclear staining and little virus at the mucosa.

Our study of this naturally occurring constellation of genetic markers has provided insights into the poorly understood phenomenon of AIV airborne transmissibility by revealing a role for NS1 and characteristics of viral replication in the URT that were associated with airborne transmission.

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