Publication Date

2007

Document Type

Thesis

Committee Members

Nancy Bigley (Advisor)

Degree Name

Master of Science (MS)

Abstract

Herpes Simplex Virus Type 1 (HSV-1) can infect the nervous system, resulting in a disease known as herpes encephalitis (HSE). Herpes encephalitis affects thousands of people each year; many cases are fatal or permanently debilitating. Approximately two thousand known cases occur in the United States each year alone (Neuroland online source). Acyclovir has been the drug of choice used to treat herpes encephalitis. Even after the administration of acyclovir, permanent neurological damage and/or death often results. Thousands of individuals would benefit by the discovery of drugs that are more effective at preventing lasting HSE damage and death. Knowledge concerning HSE infection of the brain could be advanced with the development of co-culture systems that allow for the study of one specific cell type or a subpopulation of cells during an active infection. Additional models are needed to test therapies against HSE. The majority of models that currently exist are in-vivo or primary cell line models. Even though many of these models can be used to mimic what actually occurs during herpes encephalitis infection in humans, these systems have several weaknesses. The usage of in-vivo models requires a great deal of time, preparation, funding, and care by a veterinarian staff. Primary cell lines can be difficult to isolate and maintain for long lengths of time in cell culture. Unlike primary cell lines, continuous cell lines are able to be used for longer periods of time. Many can be easily purchased from cell banks such as the American Type Culture Collection (ATCC) for a reasonable price. Continuous cell lines are easy to culture and can be used in many different types of experiments. The use of a continuous cell lines prevents animal suffering and death. The purpose of this thesis was to determine if cell lines from a C3H murine strain can accurately mimic viral production that occurs during an actual HSV-1 infection in the central nervous system. One cell line is a pure microglial cell line. Three other cell lines, derived from P19 cells, were also tested. One cell culture tested was a system composed of mixed brain cells such as neurons, astrocyte-like cells, and fibroblast-like cells. Another culture evaluated contained only neuronal cells. P19 cells were evaluated as well. The results indicate that only the microglial and mixed cell cultures supported viral production that mirrors what occurs in animal models. The neuronal cells not only failed to produce virus, but the neurons survived for less than twenty-four hours in culture after in infection with HSV-1.

Page Count

46

Department or Program

Microbiology and Immunology

Year Degree Awarded

2007

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