Low Pathogenic Avian Influenza Isolates from Wild Birds Replicate and Transmit via Contact in Ferrets without Prior Adaptation

• Type of Material: Article
• Authors: Elizabeth A. Driskell, University of Georgia; Jennifer A. Pickens, University of Georgia; Jennifer Humberd-Smith, University of Georgia; James T. Gordy, University of Georgia; Konrad C. Bradley, Emory University; David Steinhauer, Emory University; Roy D. Berghaus, University of Georgia; David E. Stallknecht, University of Georgia; Elizabeth W. Howerth, University of Georgia; Stephen Mark Tompkins, University of Georgia
• Language: English
• Date: 2012-06-01
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Driskell et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0038067
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 7
• Issue: 6
• Start Page: e38067
• End Page: e38067
• Grant/Funding Information: This work was supported by Centers for Disease Control (CDC) grant 5U19Cl00040102 and National Institutes of Health contract HHSN266200700006C.
• Keywords: Influenza viruses; Viral replication; RECEPTOR SPECIFICITY; Respiratory infections; Mammals; LOWER RESPIRATORY-TRACT; HOST-RANGE; HEMAGGLUTININ RESIDUES; Sialic acids; Ferrets; SINGLE AMINO-ACID; POLYMERASE SUBUNIT PB2; Science & Technology; HUMAN AIRWAY EPITHELIUM; Birds; GENETIC COMPATIBILITY; Multidisciplinary Sciences; Avian influenza
• Research Categories: Biology, Virology; Biology, Microbiology; Health Sciences, Pathology

Abstract

Direct transmission of avian influenza viruses to mammals has become an increasingly investigated topic during the past decade; however, isolates that have been primarily investigated are typically ones originating from human or poultry outbreaks. Currently there is minimal comparative information on the behavior of the innumerable viruses that exist in the natural wild bird host. We have previously demonstrated the capacity of numerous North American avian influenza viruses isolated from wild birds to infect and induce lesions in the respiratory tract of mice. In this study, two isolates from shorebirds that were previously examined in mice (H1N9 and H6N1 subtypes) are further examined through experimental inoculations in the ferret with analysis of viral shedding, histopathology, and antigen localization via immunohistochemistry to elucidate pathogenicity and transmission of these viruses. Using sequence analysis and glycan binding analysis, we show that these avian viruses have the typical avian influenza binding pattern, with affinity for cell glycoproteins/glycolipids having terminal sialic acid (SA) residues with α 2,3 linkage [Neu5Ac(α2,3)Gal]. Despite the lack of α2,6 linked SA binding, these AIVs productively infected both the upper and lower respiratory tract of ferrets, resulting in nasal viral shedding and pulmonary lesions with minimal morbidity. Moreover, we show that one of the viruses is able to transmit to ferrets via direct contact, despite its binding affinity for α 2,3 linked SA residues. These results demonstrate that avian influenza viruses, which are endemic in aquatic birds, can potentially infect humans and other mammals without adaptation. Finally this work highlights the need for additional study of the wild bird subset of influenza viruses in regard to surveillance, transmission, and potential for reassortment, as they have zoonotic potential.