Department of Veterinary Medicine Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/2762
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Item Development of a Multilocus Sequence Typing Scheme for Avibacterium paragallinarum(2023) Harris, Alyssa Meihua; Ghanem, Mostafa; Veterinary Medical Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Avibacterium paragallinarum (A. paragallinarum), the causative agent of the respiratory disease Infectious Coryza (IC) in chickens, has seen a rising incidence in the United States. Current strain differentiation is inadequate for detailed epidemiological analysis. The objective of this study was to develop a Multilocus sequence typing (MLST) scheme for A. paragallinarum for outbreak investigations and to offer a better tool for strain differentiation. By evaluating whole genome sequences and clinical samples, we designed PCR amplicons for eighteen gene segments, selected six genes for their nucleotide diversity and discrimination potential. The MLST was used to differentiate seventy-five samples. Our MLST showed greater discriminatory power than existing HPG2-based methods, aligning closely with adhoc core genome MLST in 75 tested sample. Our newly developed MLST scheme enables more accurate strain differentiation, allowing for better understanding of A. paragallinarum epidemiology and population structure to help prevention and control efforts worldwide.Item HEPATITIS E VIRUS MODULATES HOST FACTORS TO GENERATE A CONDUCIVE ENVIRONMENT FOR REPLICATION(2020) lin, shaoli; Zhang, Yanjin; Veterinary Medical Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Hepatitis E virus (HEV) is one of the causative agents for liver inflammation across the world. HEV infection mainly presents as acute and self-limiting hepatitis in young adults. However, it can be exacerbated to fulminant hepatitis in HEV-infected pregnant women, resulting in up to 30% case fatality. Besides, chronic HEV infection with rapid progression in immunocompromised patients has been a challenge in many countries since it was reported years ago. HEV infection is zoonotic, and human HEV strains are grouped into four major genotypes in the genus Orthohepevirus A, the family Hepeviridae. Among the four genotypes, genotype 1 and 2 are obligate human pathogens, and genotype 3 and 4 cause zoonotic infections. Due to the lack of an effective cell culture system and a proper animal model, HEV biology, virus-cell interactions, and pathogenesis are understudied. HEV is known to inhibit the innate immune response by targeting type I interferon (IFN) signaling pathway via its ORF1 products. Nevertheless, it remains largely unknown how the virus manipulates host factors to facilitate its replication. The objective of these studies was to elucidate the mechanism of HEV manipulation of host factors to generate a conducive environment for replication. Our results show that the capsid protein of HEV inhibits the IFN production to dampen the antiviral response through its N-terminal arginine-rich motif. In addition to the impairment of innate immunity, HEV proliferation requires the presence of other host factors: DDX3, an RNA helicase, and oxysterol-binding protein (OSBP), a lipid transporter. The knockdown of these two factors led to a significant reduction of HEV replication, whereas the reconstitution of these two genes restores the HEV proliferation level. The capsid protein was found to interact with the C-terminal domain of DDX3. The HEV helicase was shown to interact with OSBP and block its translocation to the Golgi apparatus. These results indicate that HEV employs multiple strategies including blocking antiviral response and recruiting host factors for its invasion and proliferation. Our data provide insights into the HEV-cell interactions and may facilitate the development of novel antiviral strategies.