Identification of H2N3 influenza A viruses from swine in the United States

Abstract

Although viruses of each of the 16 influenza A HA subtypes are potential human pathogens, only viruses of the H1, H2, and H3 subtype are known to have been successfully established in humans. H2 influenza viruses have been absent from human circulation since 1968, and as such they pose a substantial human pandemic risk. In this report, we isolate and characterize genetically similar avian/swine virus reassortant H2N3 influenza A viruses isolated from diseased swine from two farms in the United States. These viruses contained leucine at position 226 of the H2 protein, which has been associated with increased binding affinity to the mammalian alpha2,6Gal-linked sialic acid virus receptor. Correspondingly, the H2N3 viruses were able to cause disease in experimentally infected swine and mice without prior adaptation. In addition, the swine H2N3 virus was infectious and highly transmissible in swine and ferrets. Taken together, these findings suggest that the H2N3 virus has undergone some adaptation to the mammalian host and that their spread should be very closely monitored.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

Phylogenetic trees of selected influenza virus H2 (a) and N3 (b) genes based on the nucleotide sequences of the ORFs. Horizontal distance is proportional to genetic distance. The trees are rooted to A/duck/Singapore/97 H5N3 (a) and A/tern/Astrakan/775/83 H3N3 (b). Numbers below nodes represent bootstrap values from 200 replicates.

Fig. 2.

Microscopic lung sections from control and infected pigs. (a) Bronchiole in the lung of a control pig inoculated with noninfectious cell culture supernatant. Note the regular outline of the pseudostratified columnar epithelium. (b) Necrotizing bronchiolitis in the lung of a pig 3 days after inoculation with H2N3 swine influenza virus. The epithelial lining of the airway is focally disrupted by sloughing of necrotic infected cells and early reactive proliferation of the remaining epithelium. The lumen contains sloughed epithelial cells and mixed leukocytes. A small number of lymphocytes are seen infiltrating subepithelial and peribronchiolar connective tissue.