Year of Award

2014

Document Type

Dissertation

Degree Type

Doctor of Philosophy (PhD)

Other Degree Name/Area of Focus

Microbiology and Immunology

Department or School/College

Division of Biological Sciences

Committee Co-chair

Scott Wetzel, Heinz Feldmann

Commitee Members

Steve Lodmell, Jack Nunberg, Keith Parker

Keywords

Nipah virus, pathogenesis, vaccine, Virology

Abstract

Nipah virus is a zoonotic pathogen that infects a wide species range including humans. It was first discovered in Malaysia in 1998 during a large outbreak, but since has spread to Bangladesh and India causing almost yearly outbreaks in the region since 2001. The distinct geographic locations have led to two genetically varied strains. Infection of humans by Nipah virus leads to respiratory distress and acute encephalitis. Pathology caused by the virus is characterized by vasculitis, necrosis, and edema of small vessels of the lung and brain primarily. This work investigates differences of pathology and clinical signs in the hamster model between strains, aiming to explain differences seen in epidemiology reports. We also characterize infection of endothelial and smooth muscle cells, which make up the vasculature, and how they react to infection. After better understanding the pathology in vivo and in vitro, we developed and efficacy tested a single-dose Vesicular stomatitis virus based vaccine. Data from this work demonstrates that although the Bangladesh strain is delayed 2 days compared to the Malaysian strain they cause similar pathology in hamsters. We also show that Nipah virus replicated in smooth muscle cells but does not cause adverse effects. Finally this study presents a vaccine that is protective against Nipah virus pathology. Overall this work allows for future studies using the Bangladesh strain, better defines infection of primary vascular cells, and proposes a possible vaccine candidate for outbreak use.

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© Copyright 2014 Blair Lynn DeBuysscher