Using Genetic and Pathogeneses Studies to Develop Antiviral and BVDV Vaccine Targets

<p>Understanding bovine viral diarrhea virus (BVDV) interaction with the host may help explain the ability of the virus to cause multiple forms of disease ranging from subclinical symptoms to severe disease and even death. BVDV cytopathogenicity and onset of mucosal disease within one herd of PI animals were studied. Cytopathic BVDV viruses isolated from 13 of the PI animals showed a cellular DnaJ insertion in the NS2-3 junction of the viral sequences. The insertions were identical in all of cp viruses with common borders indicating that one animal likely developed a cytopathic virus that then progressively spread to the other 12 animals. We also investigated the interactions of natural killer cells (NK) cells with either the highly acute ncp BVDV 1373 strain or the mild acute BVDV 28508.5 strain. BVDV exhibited a strain effect on NK cells. NK cells phenotypic and functional markers, CD2, NKp46, CD25, and granulysin were affected differently by BVDV 1373 than BVDV 28508.5. Both strains reduced NK cell cytotoxicity function. BVDV RNA and E2 protein were detected inside NK cells after exposure to BVDV 1373 with no indication of production of infectious virus. We also explored the ability of the BVDV Npro protein to evade host immune response through interfering with host type I interferon defense mechanism. Using immunoprecipitation coupled with mass spectrophotometry BVDV 1373 Npro showed association with S100A9 protein that may play role in mechanisms of cells resistance to the virus through activating interferon type I. This study gave some evidence that mechanism of cytopathogenicity within one herd was single mutant resulted from rare Viral RNA – cellular RNA recombination. In addition, this study highlighted the role of BVDV strain effect in modifying NK cells function and phenotype. Finally, our data showed some evidence for the role of DAMPS in viral immunity and replication.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Thesis - University Access Only

Discipline thesis:degree_discipline

Veterinary and Biomedical Sciences

Year dc:date.available

2013

Author dc:creator

• Darweesh, Mahmoud

Contributors dc:contributor

• Christopher C.L. Chase

• Veterinary Infectious Diseases
• Veterinary Microbiology and Immunobiology
• Veterinary Pathology and Pathobiology

Statement dc:rights

• <p>In Copyright - Educational Use Permitted<br /><a href="http://rightsstatements.org/vocab/InC-EDU/1.0/">http://rightsstatements.org/vocab/InC-EDU/1.0/</a></p>

Language dc:language

en

Repository record dc:identifier

https://openprairie.sdstate.edu/etd/1401

OAI identifier oai:identifier

oai:openprairie.sdstate.edu:etd-2400