Neuroimmune Modulation of Virus Immunity In Aging

本提案响应主题#I 1，心理神经免疫学。疱疹病毒通常在人类中引起感染。这些感染通常以急性期为特征，伴有轻微的发病率和死亡率，随后是慢性潜伏期，反映了病毒复制和宿主免疫反应之间的平衡。疱疹病毒再激活的控制主要是由细胞免疫介导的，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。与疱疹病毒再激活相关的另一个因素是压力，已经有相当多的推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。与压力相关的免疫力下降在老年人中尤其值得关注，因为他们的细胞免疫力已经与年龄相关。对三名老年受试者的初步分析证实了疱疹病毒家族成员爱泼斯坦-巴尔病毒（EBV）的裂解复制。因此，申请人将检验衰老会降低ebv特异性细胞免疫力的假设

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.