"The Effect of Bovine Viral Diarrhea Virus on Immune Gene Expression of" by Beresabeh Tigabu

Document Type

Thesis - University Access Only

Award Date

2007

Degree Name

Doctor of Philosophy (PhD)

Department / School

Veterinary and Biomedical Sciences

Abstract

BVDV is a single stranded RNA virus of the genus Pestivirus within the family of Flaviviridae. It exists in two biotypes, cytopathic (cp) and noncytopathic (ncp), based on their ability to induce cytopathology in bovine cell cultures. BVDV has a worldwide distribution and causes a variety of disease syndromes in cattle, ranging from transient mild clinical syndromes to a fetal mucosal disease. In utero infection during early gestation with ncp virus, results in the calf becoming persistently infected and immunotolerant to the infecting virus strains and susceptible to other pathogens. BVDV is well known for its ability to cause immunosuppression and enhancing the susceptibility of the host to other pathogens. However, the exact mechanism of how BVDV impairs the immune system of the infected host is unknown. The aim of this project was to investigate the mechanisms that bovine viral diarrhea virus modulates innate immunity and cause immunosuppression in persistently infected calves Macrophages are important in host immunity as they phagocytise and kill pathogens. Although using primary macrophages in cell culture has numerous advantages, these cells undergo terminal loss of division potential as they complete their in vitro life span. Immortalized macrophage cell alleviate this problem. However, cell lines must not only be capable of extended proliferation, but also possess the same genotype, phenotype and tissue markers of their parental tissue. We investigated the phenotype and function characteristics of SV 40 transformed bovine peritoneal macrophages (BoMac) and compared them with that of monocyte derived macrophages (MDM). MDMs express typical tissue macrophage morphology, phenotype and functions. They express MHC II, CDl lb, CDl lc and CD14. They are also capable of phagocytosis. However, BoMac cell lines express only MHC I and were not able to phagocytize. To determine the effect of BVDV on innate immune receptors, we investigated the influence of BVDV in the expression of toll-like receptors (TLR). Bovine macrophages express TLRs that play an important role in pathogen recognition in the innate immune system. We used different strains of BVDV to infect MDMs from 6-36 h. The mRNA expression ofTLR-2 was downregulated in BVDV infected macrophages, however, this was not statistically significant. In addition, BVDV modestly downregulated TLR-4 expression in the first 12 h of infection in MOI dependent manner. The mechanism of immunosuppression ofBVDV infection is multifactorial. To investigate these diverse responses of the immune system to BVDV infection, we used a microarray expression profiling system. Lung leukocytes from PI and non-PI calves were used to determine gene expression profile due to BVDV infection. The group of genes which were upregulated includes pro-apoptotic genes like p53, and down regulated genes include anti-apoptotic genes and pro-inflammatory genes. This study demonstrated that multiple factors are involved in immunosuppressive effect of BVDV. It contributes to the understanding of the mechanism by which bovine diarrhea virus interfere with immune system and may also help in designing preventive and therapeutic management against BVDV infections.

Library of Congress Subject Headings

Bovine viral diarrhea virus
Cattle -- Virus diseases
Cattle -- Immunology
Leucocytes

Format

application/pdf

Number of Pages

173

Publisher

South Dakota State University

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