The Non-Structural Protein 1 of Subtype H1N1 Avian Influenza A Viruses Mediates Airborne Transmissibility in the Ferret Model.

Abstract

<p>The non-structural protein 1 (NS1) of influenza A viruses (IAVs) is a multi-functional protein that facilitates viral genome replication and antagonizes host antiviral responses. Our studies of shorebird-isolated subtype H1N1 avian influenza A viruses (AIVs) revealed a role for NS1 in airborne transmission in a ferret model of human IAV transmission. A single mutation, S213P, in the NS1 of these AIVs abrogated airborne transmission. Here we studied the host responses underlying the abrogation of airborne transmission by S213P in ferret nasal turbinates following infection with A/ruddy turnstone/Delaware/300/2009 (H1N1) (DE300), which was airborne transmissible in the ferret model. S213P in DE300 was associated with reduced pathology in the respiratory epithelium of the upper respiratory tract, the determinant anatomic site of influenza virus airborne transmission. This reduced pathology was associated with an almost absence of cellular debris and exudate that stained for influenza virus antigen in the airways of the nasal epithelium, which may mediate the formation of virus-laden particles that mediate airborne transmission. This material was abundant in animals infected with DE300 or other airborne transmissible AIVs. S213P was associated with the up-regulation of pathways regulating innate immunity and apoptosis. Overall, our study indicates that NS1 is an important mediator of the host responses in the upper respiratory tract underlying airborne transmission.</p>