Master of Science, The Ohio State University, 2022, Veterinary Preventive Medicine

Rotavirus A (RVA) is the primary cause of acute viral gastroenteritis in children and young animals globally; however, its replication and pathogenesis remain poorly understood. We have previously demonstrated contrasting modes of interactions with the host cell glycans for two prevalent porcine RVA strains: OSU G5P[7] (historically associated with severe disease in piglets) and G9P[13] (globally emerging variant in humans and swine). Specifically, OSU G5P[7] and G9P[13] strain replication was significantly decreased and significantly increased, respectively, following removal of terminal sialic acids (SA) by neuraminidase (NA) treatment. The latter contrasting effects coincided with the presence of distinct mutations found in the VP4 fusion region of these strains. In our first study, to clarify cellular mechanisms associated with these differential mechanisms of cell attachment/entry we conducted transcriptome analysis of porcine small intestinal enteroids (PIEs) infected with the two RVA strains with and without NA treatment. NA treatment of porcine intestinal enteroids alone, before individual RVA G9P[13]/OSU G5P[7] infection resulted in altered expression of genes associated with biological regulation, transporter activity, protein binding, and multicellular organismal processes. This was shown with significant contradicting impacts, with G9P[13] being significantly enhanced, and OSU G5P[7] replication being significantly inhibited. Cholesterol (a key component of the host plasma membranes) has been shown to play a critical role in RVA replication. To further improve our understanding of RVA pathogenesis taking into consideration RVA genotype-specific features, in our second study, we comparatively evaluated the effects of cholesterol and cholesterol-related additives [Methyl-β-cyclodextrin (MβCD), and diethylaminoethyl (DEAE), and bile acids (BAs)] on G9P[13] vs. OSU G5P[7] replication in vitro. Consistent with our previous findings, treatment with cholest (open full item for complete abstract)

Committee: Anastasia Vlasova (Advisor); Linda Saif (Committee Member); Qiuhong Wang (Committee Member) Subjects: Biology; Genetics; Virology