Investigation of environmental virus-host interactions: chlorpyrifos effects on Epstein-Barr virus and B-lymphocyte replication

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Katelyn Jo Miller (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Amy Adamson

Abstract: Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that infects nearly 95% of the world’s population. EBV is closely associated with many diseases, most commonly with infectious mononucleosis, though the virus is also linked to different types of cancer such as Burkitt’s lymphoma, other non-Hodgkin’s lymphomas, Hodgkin’s lymphoma, gastric carcinoma, and nasopharyngeal carcinoma. Pesticides are globally used residentially and agriculturally and have been a topic of discussion with regard to their effects on human health. Chlorpyrifos, a neurotoxic acetylcholinesterase inhibitor, has been banned for residential use in the United States since 2000. However, it is still one of the most commonly used organophosphate pesticides for agriculture. Epidemiological case studies have investigated potential associations with individuals who have occupational organophosphate exposure (such as farmers) and certain types of cancer. However, many of these studies have inconclusive or conflicting results. An understudied area of investigation is interactions of ubiquitous human viruses and other environmental factors, such as pesticides, that may promote or further exacerbate adverse human health issues. It is equally important to understand if environmental factors affect virus-host interactions and by what cellular mechanisms. This dissertation investigates the effects of chlorpyrifos and its active metabolite, chlorpyrifos-oxon, on EBV-host interactions; specifically exploring the effects on EBV and B-lymphocyte replication. Findings suggest that chlorpyrifos and chlorpyrifos-oxon exposure produce low levels of oxidative stress and DNA damage to B-lymphocyte cells to initiate cellular signaling cascades to induce cell cycle arrest. Additionally, we find that pesticide exposure affects EBV lytic replication and latency in addition to cellular targets that are involved with viral and host-cell replication and regulatory functions. Overall, our results show that the presence of EBV appears to have a protective response to cells under cytotoxic stress. Findings from this study will contribute to a better understanding of EBV-host biology and interactions in the presence of exogenous environmental factors that may be harmful to human health.

Additional Information

Publication
Dissertation
Language: English
Date: 2019
Keywords
Environmental Health Science, Pesticides, Virology, Virus-host interactions
Subjects
Epstein-Barr virus
Pesticides
Chlorpyrifos
Virology

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