ABSTRACTTHE INTRINSIC HOST FACTORS ASSOCIATED WITH INTRASPECIFIC VIRAL SHEDDING VARIATION IN LOW-PATH AVIAN INFLUENZA-INFECTED WILD DUCKSByAmanda C. Dolinski In this dissertation I, with co-authors and co-collaborators, evaluated the association between intraspecific viral shedding variation and intrinsic host factors in low-path avian influenza virus (LPAIV) infected mallards and blue-winged teals. We hypothesized that intraspecific viral shedding variation would be associated with intraspecific variation in virus receptor occurrence frequency and gene expression at the host tissue site of viral replication. Chapter one is a literature review of super-shedding effects on pathogen transmission dynamics and highlights the importance of studying super-shedding in wildlife from a zoonotic spillover and conservation perspective. Conclusions drawn include the recognition that many different wildlife host-pathogen systems exhibit intraspecific variation in pathogen load, and various techniques/technologies should be utilized for expanding current knowledge of wildlife pathogen transmission dynamics in the purpose of developing innovative wildlife disease management programs. In chapter two we evaluated the association between intraspecific variation in LPAIV load and alpha-2,3 sialic acid viral receptors (SAα2,3Gal) in the intestines and bursa of mallards and blue-winged teals. Our hypotheses were supported in that we detected a significant relationship between LPAIV load and SAα2,3Gal occurrence frequency in the ileum of mallards. SAα2,3Gal in teals did not have a significant relationship with LPAIV load; however, teals had higher virus titers and SAα2,3Gal occurrence frequency than mallards. In conclusion, we determined that higher SAα2,3Gal occurrence frequency was associated with higher virus titers and may also be a contributing host factor for intraspecific LPAIV shedding in mallards. In chapters three and four we evaluated differential gene expression in association with intraspecific individual viral shedding in wild mallards and blue-winged teals, respectively. We found that several genes of the innate immune system and pro-viral cell entry and replication were up-regulated in higher shedding LPAIV-infected birds than lower shedding birds. For both species, most of the differential gene expression was observed in the ileum compared to the bursa. Early in the infection, mallards showed most differential gene expression between viral shed level groups and teals showed most differential gene expression between LPAIV-infected and uninfected birds. Later in the infection, differential gene expression was not observed in mallards, but in teals several genes were down regulated in high shedders. We also found statistically significant positive linear relationships for expression of innate immune genes and viral shedding, but mostly early in the infection. We concluded that intraspecific LPAIV shedding variability was closely related to innate immune gene expression, and that genes which promote viral cell entry and viral replication were likely impacting viral shedding load. Chapter five is a dissertation summary where I draw conclusions based on the previous chapters, suggest hypotheses for potential mechanisms responsible for intraspecific variation in LPAIV shedding, and recommend how the dissertation data and results could be used for future research. Collectively, the research in this dissertation provides evidence that physiological, genetic, and immunogenic host factors were associated with intraspecific variation in viral shedding.
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