Reverse zoonosis of the 2022-2023 human seasonal H3N2 detected in swine

Authors: ZELLER, MICHAEL - Iowa State University; MORAES, DANIEL - Iowa State University; CIACCI ZANELLA, GIOVANA - Iowa State University; SOUZA, CARINE - Iowa State University; Anderson, Tavis; Baker, Amy; GAUGER, PHILLIP - Iowa State University

Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/4/2024
Publication Date: 8/13/2024
Citation: Zeller, M., Moraes, D., Ciacci Zanella, G., Souza, C.K., Anderson, T.K., Baker, A.L., Gauger, P.C. 2024. Reverse zoonosis of the 2022-2023 human seasonal H3N2 detected in swine. Viruses. https://doi.org/10.1038/s44298-024-00042-4.
DOI: https://doi.org/10.1038/s44298-024-00042-4

Interpretive Summary: Multiple human-to-swine spillover events of H3N2 influenza A virus (IAV) were detected by Iowa State University Veterinary Diagnostic Lab in the 2022-2023 human influenza season. These detections occurred in seven states: Colorado, Illinois, Indiana, Missouri, North Carolina, Ohio, and Pennsylvania as well as the countries of Chile and Mexico. The spillovers were derived from two genetic lineages of human seasonal H3 IAV, 3C.2a1b.2a.2b and 3C.2a1b.2a.2a.1. Multiple detections occurred in both Colorado and North Carolina, and our analysis indicated that these may have been swine-to-swine transmission. Next generation sequencing generated whole genome sequences and were used to demonstrate that the human viruses collected in pigs were cocirculating on farms that had endemic swine IAV. Two IAV isolates from the 3C.2a1b.2a.2b lineage virus were obtained. These isolates were antigenically distinct from endemic swine IAV virus but were still antigenically similar to H3 viruses that were circulating in humans between 2020 and 2023. Pigs experimentally inoculated with the isolate exhibited minimal to mild macroscopic lung lesions, but swine-to-swine transmission was not observed. These strains of H3 represent an emerging threat to swine health through the introduction of new viral diversity and should be monitored to assess whether they evolve to become more transmissible in the swine host.

Technical Abstract: The Iowa State University Veterinary Diagnostic Laboratory detected multiple human-to-swine reverse zoonosis of the 2022-2023 human seasonal H3N2 between November 2022 and November 2023. Nineteen cases from seven U.S. locations were detected: Colorado, Illinois, Indiana, Missouri, North Carolina, Ohio, and Pennsylvania. Additional cases were detected in Mexico and Chile. Virus was isolated from two nasal swab samples out of four; the remaining fifteen sample submissions were derived from oral fluids. All H3 human spillover viruses were classified to one of two human-seasonal H3 clades, 3C.2a1b.2a.2b and 3C.2a1b.2a.2a.1. Phylogenetic inference indicated at minimum 7 reverse zoonotic events occurred, with possible swine-to-swine transmission following the initial spillover. Twelve neuraminidase genes were sequenced, nine were classified as human-seasonal H3N2 lineage: the remaining were endemic swine IAV NA genes from the N2.2002B, N2.1998, or the N1.Classical lineage. The two viral isolates obtained from nasal swab samples were sequenced and were entirely human-lineage virus. Seven clinical samples associated with the spillover submissions were sequenced and revealed co-detections with H1 1A.3.3.3, with internal gene segments from both the TRIG and pandemic 2009 lineages. Serologic investigation on samples collected at swine production systems provided evidence for infection with human seasonal H3N2 from one of the farms with concurrent virologic evidence as well as four additional farms from Mexico and the United States. The swine-isolated 3C.2a1b.2a.2b H3N2 was > 3.0 AU from endemic 1990.4.A, 2010.1, and 2010.2 swine H3N2 lineages and retained antigenic similarity (1.9 AU) to a recent human seasonal H3N2 (A/Darwin/6/2021). These data demonstrated the introduced human H3 is antigenically distinct from endemic H3 circulating in swine. Pigs experimentally inoculated with a representative isolate demonstrated replication in the nose and lungs and minimal to mild macroscopic and microscopic lung lesions, but primary pigs did not transmit the virus to indirect contacts. If sustained in the pig population, this human seasonal H3 would represent the first new lineage detected in pigs this decade and present an emerging threat to swine health and production.