Author
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KAPLAN, BRYAN - Orise Fellow |
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TORCHETTI, MIA KIM - Animal And Plant Health Inspection Service (APHIS) |
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Lager, Kelly |
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WEBBY, RICHARD - St Jude Children’s Research Hospital |
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Baker, Amy |
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Submitted to: Influenza and Other Respiratory Viruses
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 7/5/2017 Publication Date: 9/1/2017 Citation: Kaplan, B.S., Torchetti, M.K., Lager, K.M., Webby, R.J., Vincent, A.L. 2017. Absence of clinical disease and contact transmission of HPAI H5NX clade 2.3.4.4 from North America in experimentally infected pigs. Influenza and Other Respiratory Viruses. 11(5):464-470. Interpretive Summary: Influenza A viruses (IAV) originating in birds can infect and cause severe disease and potentially death in pigs and humans. In 2014, a highly pathogenic avian influenza (HPAI) virus of the H5 clade 2.3.4.4, H5N8, was introduced to North America by migrating waterfowl. Introduction of H5N8 allowed for the swapping of its genetic material with other avian strains from North America, resulting in two additional subtypes, H5N1 and H5N2. The H5N2 spread across the USA, presumably by wild birds, and was isolated from poultry farms in the Midwest, resulting in millions of dollars in losses. Although there were no documented cases of H5N1, H5N2, and H5N8 in U.S. swine, understanding the risk these viruses pose to domestic pigs is important for veterinary health as the pig density is very high in the same region as the poultry detections. The risk of spillover of these HPAI viruses into swine is also important for human health as the ability to infect swine could lead to more gene swapping or changes to the virus that may allow it a greater ability to infect humans following mammalian adaptation in the swine host. We show that HPAI viruses of the new H5 clade 2.3.4.4 of the three subtypes tested pose a low risk for infection and transmission among pigs. The results of these studies are invaluable in understanding the risks posed by H5N1, H5N2, and H5N8 HPAI viruses to agriculture and public health should they return again to the USA or elsewhere in the world where they circulate. Technical Abstract: In the fall of 2014, clade 2.3.4.4 highly pathogenic avian influenza (HPAI) subtype H5N8 were introduced into North America by migrating waterfowl from Asia where, through reassortment, novel HPAI H5N2 and H5N1 viruses emerged. We sought to assess the susceptibility of pigs to North American HPAI clade 2.3.4.4 H5N1, H5N2, and H5N8. Pigs and trachea explants were inoculated with a representative panel of clade 2.3.4.4 HPAI viruses from North America. Nasal swabs, BALF, and serum were collected to assess replication and transmission in challenged and direct contact pigs by RRT-PCR, virus isolation, HI, and ELISA. Limited virus replication was restricted to the lower respiratory tract of challenged pigs, though absent in the nasal passages and trachea cultures, as determined by RRT-PCR in all samples and virus isolation from RRT-PCR positive samples. Seroconversion of inoculated pigs was detected by NP ELISA but was not reliably detected by antigen specific HI. Boost with adjuvanted-virus was required for the production of neutralizing antibodies to assess cross-reactivity between wild-type avian strains. All RRT-PCR and serology tests were negative for contact animals indicating a failure of transmission from primary inoculated pigs. Clade 2.3.4.4 H5NX strains can replicate in the lower respiratory tract of swine upon high titer inoculation, though appear to be incapable of replication in swine nasal epithelium in vivo or ex vivo in trachea explants in culture. Infected pigs do not produce high levels of neutralizing antibodies following infection. Collectively, our data show clade 2.3.4.4 HPAI H5NX viruses to be poorly adapted for replication and transmission in swine. |
