Leyson, C. | Search bioRxiv

bioRxiv2025

Viral lineage and mode of exposure modulate within host spatial dynamics of influenza A viruses

The upper and lower respiratory tracts (URT and LRT) present distinct environments for influenza A virus (IAV) replication. Their differential features have major implications for viral evolutionary dynamics, transmission potential, and pathogenesis. To investigate the implications of differential viral replication in the URT and LRT, we assessed dispersal of IAVs throughout the guinea pig respiratory system. Guinea pigs were inoculated intranasally with a 300 L volume to deliver inoculum to both the URT and LRT. Two strains were used to represent the circulating seasonal IAV lineages: influenza A/TX/50/2012 (H3N2) and influenza A/CA/07/2009 (H1N1) virus. The inclusion of a diverse genetic barcode enabled high-resolution tracing of viral dispersal for the H1N1 virus. While infectious virus was consistently detected in the URT, the H1N1 virus could be detected in LRT while the H3N2 virus could not. To determine whether replication of the H1N1 virus in the LRT extends to other modes of infection, virus distribution was evaluated following infection via aerosol exposure or transmission. Infectious virus in lung homogenates was observed in both cases, confirming the LRT tropism of the H1N1 virus. Sequencing genetic barcodes revealed that diversity was largely maintained in nasal samples and trachea but contracted upon dispersal to the lungs. This loss of diversity was associated with increased distance to and branching from the major airways, implicating long distance dispersal through the airways in imposing within-host population bottlenecks. These data underline the implications for within-host viral dynamics of the distinct environments of the upper and lower respiratory tracts. ImportanceThe upper (URT) and lower (LRT) respiratory tracts create different conditions for influenza A virus (IAV) spread and evolution. We studied how the virus moves through guinea pigs airways after infection with H3N2 or H1N1 strains of IAV. Whether delivered intranasally, by aerosol or by transmission, the H1N1 virus replicated in the nasal cavity, trachea, and lungs. By contrast, the H3N2 virus stayed mostly in the nasal cavity. Genetic barcodes were used to track how the H1N1 virus moved and changed. The populations replicating in the nasal cavity and trachea maintained high diversity but those sampled from the lungs showed low diversity. This bottlenecking effect was stronger for viral populations present deeper in the lungs. These findings show that the different environments of the URT and LRT strongly shape how influenza spreads and evolves inside a host.

microbiology↗

bioRxiv2024

A systematic review of laboratory investigations into the pathogenesis of avian influenza viruses in wild avifauna of North America

The lack of consolidated information regarding wild bird species response to avian influenza virus (AIV) infection is a challenge for conservation managers, researchers, and related sectors such as public health and commercial poultry. Such information could be used to model complex disease dynamics within communities, prioritize species for surveillance and conservation efforts, or identify species more likely to facilitate spillover into domestic animals or humans. Using two independent searches, we reviewed published literature for studies describing wild bird species experimentally infected with avian influenza to assess host species relative susceptibility to AIVs. Additionally, we summarized broad-scale parameters for elements such as shedding duration and minimum infectious dose that can be used in transmission modeling efforts. Our synthesis documented that waterfowl (i.e., Anatidae) comprise the vast majority of published AIV pathobiology studies, whereas gulls and passerines were less represented in research despite evidence that they also are susceptible and contribute to high pathogenicity avian influenza disease dynamics. This study represents the first comprehensive effort to compile available literature regarding the pathobiology of AIVs in all wild birds in over a decade. This database provides an opportunity to critically examine and assess what is known and identify where further insight is needed.

ecology↗