Date on Master's Thesis/Doctoral Dissertation
12-2014
Document Type
Master's Thesis
Degree Name
M.S.
Department
Pharmacology and Toxicology
Committee Chair
Jonsson, Colleen B.
Committee Co-Chair (if applicable)
Arteel, Gavin E.
Committee Member
Lukashevich, Igor S.
Committee Member
Palmer, Kenneth E.
Committee Member
Remold, Susanna K.
Subject
Hantaviruses; Virology
Abstract
Hantaviruses, family Bunyaviridae, are present throughout the globe in a variety of mouse, rat, mole, vole, shrew, or bat species. Hantaviruses persist for the lifetime of the animal reservoir, while causing no signs or symptoms of disease. Only the rodent-borne hantaviruses cause disease in humans. In contrast, a “spillover” infection of a hantavirus into a nonreservoir rodent species results in an asymptomatic acute infection. We and others in the field are interested in understanding the biology of these virus-host interactions and mechanisms that underlie these three very different outcomes. The second chapter of my thesis focused on probing the intrahost viral population structure of the Hantaan virus (HTNV), an Old World hantavirus, in the suckling mouse model in the presence and absence of ribavirin. This model represents a lethal disease outcome in a nonreservoir species. These studies show, for the first time, two distinct evolutionary trajectories for HTNV within this lethal mouse model of disease in the presence and absence of ribavirin, as well as evidence for positive selection not previously observed in vitro. In the ribavirin-treated vRNA population, analyses of rates of nonsynonymous (dN) and synonymous (dS) substitutions in the S-segment revealed a positive selection for codons within the HTNV N protein gene, while untreated, HTNV-infected mice showed purifying selection. The third chapter of my thesis focused on development of a physiologically relevant, in vitro model of the hantavirus-rodent reservoir interaction; specifically, the deer mouse (Peromyscus maniculatus) and Sin Nombre virus. As the primary target of hantaviral infection is the vascular endothelium, a primary lung microvascular endothelial cell (L-MVEC) culture system was established. Culture conditions were established and optimized for passage and infection. Future research will use this model to probe viral determinants and mechanisms that promote persistence and identify host responses that pose barriers to virus adaptation.
Recommended Citation
McAllister, Ryan Carroll 1988-, "Development of models for the study of the molecular mechanisms of host restriction and adaptation of hantaviruses." (2014). Electronic Theses and Dissertations. Paper 1780.
https://doi.org/10.18297/etd/1780
