Exploring the human-swine interface of influenza A viruses

Hennig, Christin (2024): Exploring the human-swine interface of influenza A viruses. Dissertation, LMU München: Tierärztliche Fakultät

Abstract

The COVID-19 pandemic has highlighted the significance of closely monitoring emerging infectious diseases, as 75% of them originate from animals. Influenza A viruses (IAV) have repeatedly proven to be an imminent global health threat over the last century by provoking five human pandemics, that have been mostly traced down to originate from an animal source. In general, IAVs are host specific, but remain genetically highly flexible due to their error-prone RNA polymerase (genetic drift) and their segmented genome structure, which can lead to reassortment between different IAV strains (genetic shift). Thus, IAVs are able to overcome host-restriction factors and evade innate immune response of novel host environments, which leads to frequent inter-species spillover events. Swine influenza A virus (swIAV) is present in pig populations globally, causing harm to animal welfare and resulting in economic losses as a part of the porcine respiratory disease complex (PRDC). The subtypes H1N1, H1N2 and H3N2 circulate enzootically in pig herds, leading to respiratory disease and, indirectly, reproductive losses. After suspecting pigs as a reservoir for zoonotic IAV, the emergence of the H1N1pdm09 “Swine flu” in 2009 in Mesoamerica became the latest human pandemic and underlined this assumption. H1N1pdm09 as well as other seasonal human IAV were repeatedly introduced by humans into pig populations worldwide by reverse zoonosis. These events have led to a drastic increase of genetic swIAV diversity, with the establishment of potential zoonotic reassortants in pig holdings. The industrialization of pork production and the increasing cross-border trade in recent decades have created a growing interface between humans and swine, which may facilitate reciprocal transmissions of IAV. Sporadic and clustered outbreaks of zoonotic swIAV have been observed regularly worldwide, but without establishing sustained human-to-human transmission chains yet. However, it was observed, that persons with occupational exposure to swine have a heightened seroprevalence for swIAV compared to the general human population, considering them to have an increased risk to exposure of potential zoonotic swIAV. To gain a comprehensive understanding of the complexity of host-specific factors and disease dynamics of interspecies transmission of IAV at the human-swine interface, a One Health approach was employed in this thesis. Therefore, (i) we revised the role of pigs as reservoirs for zoonotic IAVs and analyzed the latest zoonotic spillover events globally, (ii) updated diagnostic tools to improve swIAV surveillance and analyzed swIAV sequences to track the ongoing genomic diversification and identify zoonotic markers and (iii) explored the human-swine interface to determine the actual frequency of interspecies transmission and analyzed the potential of farm workers and children to spread swIAV in the society.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 590 Tiere (Zoologie)
• Fakultäten: Tierärztliche Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 6. Juli 2024
• 1. Bericht­erstatter:in: Meißner, Markus