We have identified a new class of pathogen-associated molecular pattern (PAMP) proteins (deoxyuridine triphosphate nucleotidohydrolases; dUTPases) that have novel immunoregulatory and neuroregulatory functions that may contribute to the pathophysiology of diseases caused by human herpesviruses. Using the Epstein-Barr virus (EBV)- dUTPase as the prototype, our pioneering studies have demonstrated conclusively that the EBV-dUTPase induces sickness and anxiety behavior and impaired learning/memory effects independent of its enzymatic activity. Furthermore, the properties of the EBV- dUTPase were enhanced by stress. This multidisciplinary research grant will provide new information on the mechanism by which stress can impact the EBV-dUTPase-mediated effects as it relates to chronic fatigue syndrome.

Public Health Relevance

We have identified a new class of pathogen-associated molecular pattern (PAMP) proteins (deoxyuridine triphosphate nucleotidohydrolases; dUTPases) that have novel immunoregulatory and neuroregulatory functions that may contribute to the pathophysiology of diseases caused by human herpesviruses. Using the Epstein-Barr virus (EBV)- dUTPase as the prototype, our pioneering studies have demonstrated conclusively that the EBV-dUTPase induces sickness and anxiety behavior and impaired learning/memory effects independent of its enzymatic activity. Furthermore, the properties of the EBV- dUTPase were enhanced by stress. This multidisciplinary research grant will provide new information on the mechanism by which stress can impact the EBV-dUTPase-mediated effects as it relates to chronic fatigue syndrome.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI084898-09
Application #
9460352
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Beisel, Christopher E
Project Start
2010-04-15
Project End
2020-03-31
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
9
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Ohio State University
Department
Genetics
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
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Saito, Toshie; Miyagawa, Kazuya; Chen, Shih-Yu et al. (2017) Upregulation of Human Endogenous Retrovirus-K Is Linked to Immunity and Inflammation in Pulmonary Arterial Hypertension. Circulation 136:1920-1935
Williams, Marshall V; Cox, Brandon; Ariza, Maria Eugenia (2016) Herpesviruses dUTPases: A New Family of Pathogen-Associated Molecular Pattern (PAMP) Proteins with Implications for Human Disease. Pathogens 6:
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Aubrecht, Taryn G; Weil, Zachary M; Ariza, Maria Eugenia et al. (2014) Epstein-Barr virus (EBV)-encoded dUTPase and chronic restraint induce impaired learning and memory and sickness responses. Physiol Behav 137:18-24
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Ariza, Maria Eugenia; Rivailler, Pierre; Glaser, Ronald et al. (2013) Epstein-Barr virus encoded dUTPase containing exosomes modulate innate and adaptive immune responses in human dendritic cells and peripheral blood mononuclear cells. PLoS One 8:e69827
Lerner, A Martin; Ariza, Maria E; Williams, Marshall et al. (2012) Antibody to Epstein-Barr virus deoxyuridine triphosphate nucleotidohydrolase and deoxyribonucleotide polymerase in a chronic fatigue syndrome subset. PLoS One 7:e47891
Christian, Lisa M; Iams, Jay D; Porter, Kyle et al. (2012) Epstein-Barr virus reactivation during pregnancy and postpartum: effects of race and racial discrimination. Brain Behav Immun 26:1280-7