Document Type

Dissertation - Open Access

Award Date

2013

Degree Name

Doctor of Philosophy (PhD)

Department

Veterinary and Biomedical Sciences

First Advisor

Christopher C. L. Chase

Abstract

Bovine viral diarrhea viruse (BVDV) causes immunosuppression and persistent infection that are great threats to the health of cattle. Antigen presenting cells (APC), like dendritic cells (DC), provide active surveillance and present antigens to the immune system. Monocyte-derived dendrite cells (MDDC) were used as an in vitro model to evaluate the effect of BVDV on DC cell surface markers expression and the role of DC in BVDV dissemination. The study used 4 different strains of BVDV: severe acute noncytopathic (ncp) BVDV2a-1373, mild acute ncpBVDV2a-28508-5, and type1b mucosal disease virus pair, cytopathic (cp) TGAC or ncp TGAN strains. MDDC did not produce infectious virus. However viral RNA was replicated and translated into the NS5a viral protein. The MDDC precursor, monocytes were infected and produced infectious BVDV. The infectious BVDV production was reduced over time as the monocyte differentiated to MDDC and virus production was completely lost by 120 hr of differentiation. The cp-BVDV1b-TGAC up regulated the MHCI, MHCII and CD86 expression while the three ncp BVDV strains reduced the MHCI, MHCII and CD86 expression in MDDC. The role of BVDV infection in autophagy induction and effect of autophagy in BVDV replication was examined. BVDV infection induced autophagy in MDBK cells and Bt cells. There was no significant difference between cp or ncp strains of BVDV in autophagosome formation. The autophagy inducing drug, rapamycin, enhanced the viral replication while the autophagy inhibiting drug, 3MA (3-Methyladenine), suppressed viral replication. The co-localization study, using BVDV NS5A or E1 with GFP-LC3 revealed that BVDV did not replicate in autophagosomes. The effect of cp or ncp BVDV infection in vivo on immune polarization to T helper-2 (TH2) or T helper-1 (TH1) by measuring serum IgG1 and IgG2 concentrations was done using the TGAC-TGAN virus pair. Ncp TGAN directed the immune response toward a TH1 or cellular immune response while the TGAC cytopathic strain of BVDV directed the immune response toward TH2 or humoral immune response. The cumulative findings of these studies contributed to the general body of knowledge regarding immunosuppression associated with BVDV infections.

Library of Congress Subject Headings

Bovine viral diarrhea virus
Cattle--Virus diseases
Antigen presenting cells
Dendritic cells

Description

Includes bibliographical references

Format

application/pdf

Number of Pages

284

Publisher

South Dakota State University

Rights

In Copyright - Educational Use Permitted
http://rightsstatements.org/vocab/InC-EDU/1.0/

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