Anishia Wasberg: Of Mice, Birds and Men: Emerging Zoonotic RNA Viruses in Birds and Small Mammals

Abstract

Segmented RNA viruses such as influenza A virus (IAV) and hantaviruses, pose significant threats to public health and animal populations due to their ability to rapidly adapt to new hosts. This thesis examines the roles of reassortment potential, genetic compatibility, and host adaptation in the evolution and emergence of these viruses, specifically focusing on avian influenza virus (AIV) in poultry and wild birds, as well as hantaviruses in small mammal reservoirs in Sweden. Genetic reassortment is crucial for IAV evolution, contributing to the emergence of novel subtypes with distinct phenotypic traits, host adaptation, and zoonotic risk potential. The globally circulating low pathogenic H9N2 IAV has repeatedly served as a genetic donor of internal gene segments, driving the emergence of novel subtypes. Using a reverse genetic system, we investigated the reassortant compatibility of poultry-adapted H9N2 and wild bird-derived hemagglutinins (HA) and neuraminidases (NA). Our findings indicate that poultry-adapted H9N2 (G1 lineage) has broad genetic compatibility with HA and NA segments of wild bird-origin IAVs. However, reassortment success does not necessarily correlate with improved replication in vitro. In our experiments, recombinant viruses generally displayed reduced replication efficiency compared to parental H9N2, although specific combinations, particularly with H2, H11, and certain H9 segments showed enhanced replication in avian or human cells. Notably, deletions in the NA stalk, a common adaptation seen in poultry, augmented replication in mammalian cells, underscoring the potential for reassortment to produce viruses with increased zoonotic risk. These findings emphasize the importance of ongoing surveillance and functional evaluation of H9N2 and co-circulating subtypes to identify emerging threats early. The thesis further investigates the geographic distribution and genetic diversity of hantaviruses in southern and central Sweden, concentrating on rodent-borne and shrew-borne variants. In Scania, Puumala orthohantavirus was found in bank voles (Clethrionomys glareolus) near human nephropathia epidemica cases, indicating a southward expansion of this virus. Phylogenetic analysis placed this strain within the Finnish lineage, suggesting a likely introduction from Finland or Karelia. In common shrews (Sorex araneus), Altai virus (ALTV) and Seewis virus (SWSV) were for the first time identified in central Sweden. This indicates co-circulation of ALTV and SWSV, highlighting shrews' role as hantavirus reservoirs. These findings enhance our understanding of hantavirus diversity and spread in Sweden and underscore the need for continued surveillance to assess the associated zoonotic risks.