Stress Effects on Virus Protein induced Inflammation and Sickness Behavior

 描述(申请人提供)：我们已经确定了一类新的病原体相关分子模式(PAMP)蛋白(脱氧尿苷三磷酸核苷酸水解酶；dUTP酶)，它们具有新的免疫调节和神经调节功能，可能与人类疱疹病毒引起的疾病的病理生理有关。以Epstein-Barr病毒(EBV)-dUTPase为原型，我们的开创性研究最终证明，EBV-dUTPase可诱导疾病和焦虑行为，并独立于其酶活性而损害学习/记忆效果。此外，EBV-dUTPase的性质在应激条件下也得到了增强。这一多学科的研究拨款将提供关于压力影响EBV-dUTPase介导的效应的机制的新信息，因为它与慢性疲劳综合征有关。

 DESCRIPTION (provided by applicant): 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.