UMD Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/3
New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a given thesis/dissertation in DRUM.
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Item Zoonotic Transmission of Influenza H9 subtype through Reassortment(2013) Kimble, James Brian; Perez, Daniel R; Cell Biology & Molecular Genetics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Influenza A virus causes disease across a broad host range including avian and mammalian species. Most influenza viruses are found in wild aquatic birds, are of low consequence and refrain from zoonotic transmission. However, some strains occasionally cross the species barrier, into domestic birds and a plethora of mammalian species, most notably swine and humans. Many of these infections are dead ends and quickly disappear from the species, but occasionally, a stable lineage is established and becomes endemic in an animal population. Avian Influenza virus (AIV) H9N2 was predominantly found in wild ducks and shore birds across the globe with occasional infections in turkeys until the late 1980's, at which point the virus became established in Eurasian poultry populations. In the late 1990's the virus again jumped hosts, first into swine, and then into humans. Across many regions, these viruses appear to be gaining human-like virus characteristics. Here, the influenza receptor distribution in a range of poultry species has been characterized and shown that many of the birds were able to bind human-like binding viruses. While no large-scale H9N2 human infections have occurred, the threat is there. The most likely route for this to occur is through reassortment with human viruses. The 2009 human pandemic H1N1 (pH1N1) is a likely candidate as it is found in multiple species and seems to readily reassort. The two viruses were shown to be compatible for reassortment and H9:pH1N1 viruses would readily infect and transmit in both ferrets (a human model animal) and swine. Finally, a novel method of modeling reassortment in vivo was developed, which simultaneously tests the breadth of possible reassortant and utilizes natural host selective pressure to select the most-fit progeny. Furthermore, the characterization of these viruses in ferrets showed they readily infect, efficiently transmit, and exhibit mild to moderate pathological consequences. Taken together, these findings broaden our understanding of natural observations, characterize the potential for zoonosis, highlight the dangers H9 viruses may pose to humans, and give scientists a new tool to deepen our understanding of reassortment.Item Molecular markers of interspecies transmission of H2N2 and H9N2 avian influenza A viruses(2008-11-19) Sorrell, Erin Maureen; Perez, Daniel R; Animal Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Most avian influenza viruses do not replicate or transmit efficiently in mammals. The events that lead to interspecies transmission and host adaptation are unknown. Part one of this project set out to establish quail as an intermediate host of influenza. Our results indicate that adapting a mallard H2N2 virus in quail leads to expanded host range in chickens. The molecular changes, which occur during the adaptation in quail, are crucial for viral replication and transmission in chickens. Further adaptation of this quail-adapted virus in chickens leads to a 27 amino acid-deletion in the stalk region of the NA, changing the tissue tropism and temperature phenotype of the virus. H9N2 influenza viruses have created in poultry an endemic situation in much of Asia, Europe and the Middle East. This subtype, albeit low pathogenic, carries with it human receptor specificity and the ability to infect humans without prior adaptation. The generation of an influenza pandemic requires interspecies transmission of a novel strain, which can adapt to its new host through either reassortment or point mutations. Given that two previous pandemics were the result of reassortment between low pathogenic avian viruses and human subtypes of that period, and given the endemic situation of avian H9N2 viruses in Eurasia, for part two of this project, we wanted to determine if adaptation of an avian-human H9N2 reassortant in ferrets could support mammalian respiratory droplet transmission. Here we show for the first time that a reassortant virus carrying the HA and NA of an avian H9N2 virus can transmit in respiratory droplets. This is the first report of respiratory droplet transmission of H9N2 influenza, which carries profound implications for pandemic preparedness. The amino acid changes on the HA might identify critical, adaptive mutations necessary for respiratory transmission in subsequent pandemic avian influenza strains. Using reverse genetics we identified key combinations of this adapted reassortant that support respiratory droplet transmission.