Submitted to: Proceedings of the National Academy of Sciences(PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/15/2007
Publication Date: 12/26/2007
Citation: Ma, W., Vincent, A.L., Gramer, M.R., Brockwell, C.B., Lager, K.M., Janke, B.H., Gauger, P.C., Patnayak, D.P., Webby, R.J., Richt, J.A. 2007. Identification of H2N3 influenza A viruses from swine in the United States. Proceedings of the National Academy of Sciences. 104(52):20949-20954.
Interpretive Summary: Influenza A virus can infect different mammalian animals. Pigs have been suggested to be the mixing vessel for avian and human influenza viruses because the porcine trachea contains binding receptors with preferences for human and avian influenza viruses. In the pig, genetic reassortment to create novel influenza subtypes by mixing avian, human and swine influenza viruses is possible. Here, we report the characterization of two novel reassortant H2N3 viruses isolated from pigs with respiratory disease. Molecular and phylogenetic analyses of these viruses revealed that the HA segment is similar to an avian influenza virus (AIV) H2N3 isolated from mallards and the NA sequence is similar to an AIV H4N3 isolated from blue-winged teal. The HA protein revealed a Q226L mutation when compared with the putative parental avian HA protein, indicating a preferential binding to SA'2,6Gal, the mammalian influenza receptor. All internal genes except PA were similar to influenza virus gene segments found in contemporary triple reassortant (human, swine, avian) SIVs in the United States. The PA segment has high homology to the PA of an AIV H6N5 isolated from mallards. Experimental infection of swine showed that the H2N3 virus is virulent for pigs, replicating in the lung and causing macroscopic and microscopic lung lesions. All experimentally inoculated pigs seroconverted to H2N3 and seroconversion was demonstrated in sentinel contact pigs as well. In addition, the H2N3 virus infected mice, inducing lung lesions, clinical disease and death. The H2N3 virus also infected ferrets and transmitted efficiently to contact sentinel ferrets. These data indicate that the novel reassortant H2N3 subtype virus has the ability to infect various mammalian hosts, suggesting a potential to transmit to humans.
Technical Abstract: Influenza viruses of the H2N3 subtype have not previously been isolated from swine. Here we characterize genetically similar reassortant H2N3 viruses isolated from pigs from two farms in the U.S. Molecular and phylogenetic analysis revealed that the HA, NA, and PA gene segments are similar to those of avian influenza viruses of the American lineage, whereas other segments are similar to those of contemporary swine influenza viruses. A leucine at HA position 226 indicates preferential binding to the mammalian virus receptor. The H2N3 virus was able to replicate in pigs, mice, and ferrets and transmissible among pigs and ferrets. Our findings indicate these H2N3 viruses can infect various mammalian hosts without adaptation, suggesting they may be transmissible to humans. Therefore, they appear to have pandemic potential and warrant close monitoring.