Neuroimmune Modulation of Virus Immunity In Aging

这项提议是对话题#1，心理神经免疫学的回应。疱疹病毒通常会感染人类。这些感染的特点通常是伴随轻微发病率和死亡率的急性期，然后是反映病毒复制和宿主免疫反应之间平衡的慢性潜伏期。控制疱疹病毒的重新激活主要是由细胞免疫调节的，细胞免疫随着年龄的增长而下降。因此，疱疹病毒感染是老年人的重要病原体，给卫生保健系统带来了相当大的成本。与疱疹病毒重新激活相关的另一个因素是压力，有相当多的猜测将压力与疱疹病毒感染的外观、持续时间和强度联系起来。与压力相关的免疫功能下降在老年人中尤其令人担忧，因为他们已经出现了与年龄相关的细胞免疫功能下降。对三名老年受试者的初步分析表明，EB病毒(EBV)可裂解复制，EBV是疱疹病毒家族的成员。因此，申请者将检验衰老会降低EBV特异性细胞免疫的假设。 并增加潜伏的EBV的重新激活。此外，压力会导致更高的病毒载量。重要的是，人们对EBV在衰老中的免疫生物学知之甚少。这项建议中概述的研究将提供与年龄相关的疱疹病毒特异性T细胞免疫下降和随后潜伏的病毒重新激活的初步数据。这些数据随后将被用于支持R01应用程序，以开发一项关于神经内分泌激素如何调节老年人疱疹病毒特异性免疫的机械性调查。

This proposal is responsive to topic #I 1, Psychoneuroimmunology. Herpesviruses commonly establish infections in humans. These infections are usually characterized by an acute phase associated with minor morbidity and mortality followed by a chronic latent phase reflecting a balance between viral replication and the host immune response. Control over herpesvirus reactivation is primarily mediated by cellular immunity which declines with advancing age. As a result, herpesvirus infections are important pathogens in the elderly and result in considerable cost to the health care system. Another factor associated with herpesvirus reactivation is stress, and there has been considerable speculation linking stress and the appearance, duration, and intensity of herpesvirus infections. The immunological decrements associated with stress are of particular concern in the elderly because they already have age-related reductions in cellular immunity. Preliminary analysis of three elderly subjects has demonstrated lytic replication of Epstein-Barr virus (EBV), a member of the herpesvirus family. Therefore, the applicant will test the hypothesis that aging will decrease EBV-specific cellular immunity and increase reactivation of latent EBV. Furthermore, stress will result in higher viral load. Importantly, little is known about the immunobiology of EBV in aging. Studies outlined in this proposal will provide preliminary data regarding age-related declines in herpesvirus-specific T-cell immunity and subsequent latent virus reactivation. These data will subsequently be used to support an R01 application to develop a mechanistic investigation on how neuroendocrine hormones modulate herpesvirus-specific immunity in the elderly.