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INVESTIGATOR: Webb, B. T.

PERFORMING INSTITUTION:
NORTH DAKOTA STATE UNIV
FARGO, NORTH DAKOTA 58105

IN UTERO INFECTION WITH BOVINE VIRAL DIARRHEA VIRUS IMPAIRS FETAL BONE DEVELOPMENT

NON-TECHNICAL SUMMARY: Bovine Viral Diarrhea Virus (BVDV) causes a wide range of clinical manifestations in cattle, which include infertility, abortion, stillbirth, birth of weak calves and suppression of the immune system, which secondarily leads to infection by other disease agents. BVDV, which infects cattle populations throughout the USA and world, causes significant economic losses to the cattle industry making it arguably the most important viral disease of cattle. The research examines transplacental infection with BVDV, which leads to persistent infection (PI) of the fetus and life-long shedding of virus. The latter is responsible for maintaining the virus in cattle populations. PI negatively impacts the developing fetus often leading to a myriad of developmental abnormalities including abnormal long bone development, which is the main focus of this research. Abnormalities of the long bones caused by PI with BVDV are characterized by an excessive accumulation of bone, known as osteopetrosis which results from impaired bone resorption. Resorption of bone is mediated by bone resorbing cells known as osteoclasts, which share a common precursor cell with an important type of white blood cell called monocytes or macrophages. The research tests the hypotheses that long bone abnormalities in PI fetuses are caused by decreased bone resorption due to impaired differentiation or development of osteoclast from precursor cells. The studies will address gaps in knowledge concerning the mechanisms by which PI with BVDV impacts osteoclast and immune cell precursor development. Summarily, the information gained from these studies has promise to impact the knowledge base of how this economically important virus causes disease.

OBJECTIVES: The objectives of the research are to define the exact character of the long bone lesions and the cellular and molecular mechanisms underlying lesion development in fetuses persistently infected (PI) with Bovine Viral Diarrhea Virus. Specifically, the research aims to: 1) quantitatively determine the relative contributions of formation and resorption processes in the development of bone lesions on Days 175 to 185 of gestation and 2) systematically evaluate the effect of PI on osteoclast differentiation, precursor cell proliferation, and osteoclast function in vitro.