Title

Bovine Viral Diarrhea Virus: Biotypes and their Contribution to Pathogenesis of the Disease in Susceptible Cells

Advisor

Pinchuk, Lesya M.

Committee Member

McCarthy, Fiona M

Committee Member

Pharr, G. Todd

Committee Member

Nanduri, Bindu

Committee Member

Lawrance, Mark L.

Date of Degree

1-1-2012

Original embargo terms

MSU Only Indefinitely

Document Type

Dissertation - Open Access

Major

Veterinary Medical Science

Degree Name

Doctor of Philosophy

College

College of Veterinary Medicine

Abstract

Bovine Viral Diarrhea Virus (BVDV) is a significant disease causing agent with major economic impact on the cattle industry, causing both productive and reproductive losses. One reason for its widespread distribution is that the majority of all BVDV infections occur without clinical signs, leaving most cases of BVDV undetected in cow herds. BVDV occur as cytopathic (CP) or non-cytopathic (NCP) biotypes, classified according to whether or not they produce visible changes in cell culture. CP BVDV biotype but not NCP biotype is implicated in the induction of apoptosis in vivo. The interaction of BVDV with its host has several unique features, most notably the capacity to infect its host either transiently or persistently. The pathogenesis of the disease caused by BVDV is complicated and interaction between BVDV and the host are poorly understood. The overall goal of this research is to identify mechanistic pathways that govern the outcome of BVDV infection in susceptible host cells. Specific aspects of this goal is to understand BVDV biotypes-induced changes on cellular proteome, cell death and survival mechanisms used by BVDV biotypes in apoptosis pathway, interactions of BVDV NS3 viral protein with host cellular proteins and how BVDV cell entry and infection interfere with an early step of professional antigen presentation, antigen uptake. The results of this work showed, for the first time, the successful use of proteomics in studying BVDV-host interactions in a comprehensive approach. Using the Gene Ontology and systems biology analysis we identified biotype-related differences in significant biological pathways and functions. Also, using a proteomics approach, we identified multiple critical cellular proteins that interact with CP NS3 viral protein at multiple stages of CP BVDV replication cycle. This project provides insight into the cellular pathways and functions involved in the viral cytopathogenicity of CP BVDV biotype. In addition, our data not only confirmed the previous observations on the critical involvement of the intrinsic pathway of apoptosis in CP BVDV infection, it also identified multiple mitochondrial and antioxidant proteins contributing to this pathway. Finally, we show that BVDV exploit selective antigen uptake mechanisms in professional antigen presenting cells monocytes during viral entry.

URI

https://hdl.handle.net/11668/19729

This document is currently not available here.

Share

COinS