CYTOMEGALOVIRUS INFECTION FOLLOWING BONE MARROW TRANSPLANTATION

巨细胞病毒(CMV)感染是最常见的感染原因 骨髓移植(BMT)后死亡的风险。预防和控制 由这种感染引起的疾病需要了解CMV是如何 获得性感染，因为一些患者重新激活了潜伏感染，而另一些患者 感染来自外源，特别是血液制品 或来自之前接触过CMV的捐赠者的骨髓。长期的 当前提案的目标是澄清CMV 发生感染时，要寻找能够区分电流的实验室标志物 (或预测巨细胞病毒病的发展)从无症状感染，以及 加强对巨细胞病毒病和感染的预防和治疗 适用于骨髓移植后的患者。为此，有以下具体目标和 建议进行以下研究：1)明确病毒血症在预测CMV中的作用 疾病。将使用技术来实现快速检测(通过CMV 抗原血症试验)和病毒与血液相互作用的特征 骨髓移植后患者的细胞。感染的特定血细胞将被 鉴定，鉴定特定病毒mRNAs和蛋白质的表达， 这些观察结果与临床结果相关。这些研究 可能会确定预测哪些患者将留下来的特征 无症状，并会发展成CMV对组织的损害。2)至 表征病毒与肺细胞的相互作用(通过 支气管肺泡灌洗(BAL)、病毒mRNAs和蛋白质模式 BAL细胞中的表达将与患者的临床病程进行比较 遵循BMT，努力确定当前或预测因素的指标 关于未来发展的CMV间质性肺炎，最具破坏性的 这种感染的并发症。3)确定骨髓的作用 在传播巨细胞病毒时的供体。来自供者骨髓的CMV个体毒株 将使用分子技术进行鉴定并与菌株进行比较 导致骨髓移植受者的骨髓移植后感染。这些研究应该 阐明骨髓捐赠者的作用，但也可能揭示 血液制品、骨髓捐献者和重新激活的相对重要性 来自受体的内源性病毒在引起巨细胞病毒感染和疾病。 这些研究可以预测预防措施的成功(例如， 将血清阴性的血液产品提供给血清阳性的接受者) 学习。4)研究预防措施和早期干预的效果。 预防巨细胞病毒病的干预。随机化研究 化学免疫预防(针对血清阳性者)和血液产品 提出了(针对血清阴性个体的)操纵。对于所有这些 来自前三个目标的研究和实验室调查将相互关联 带着结果。将使用快速检测病毒血症(目标1)作为一种手段 识别早期病毒血症，然后进行治疗，试图预防 巨细胞病毒病的发展。这些研究代表了一个全面的 确定有效预防措施的方法，用于确定CMV的预测因素 疾病，并澄清病毒传播的方法。这应该是 有助于更好地了解病毒与宿主的相互作用 更好的预防和早期治疗病毒感染的方法。

Cytomegalovirus (CMV) infection has been the most frequent infectious cause of death following bone marrow transplantation (BMT). Prevention of the disease caused by this infection requires understanding of how CMV is acquired, since some patients reactivate latent infection while others acquire the infection from exogenous sources, in particular blood products or bone marrow from donors previously exposed to CMV. The long-term objectives of the current proposal are to clarify the methods by which CMV infection occurs, to seek laboratory markers which can distinguish current (or predict development of CMV disease) from asymptomatic infection, and finally to improve prophylaxis and treatment of CMV disease and infections for patients following BMT. To this end, the following specific aims and studies are proposed: 1) To define the role of viremia in predicting CMV disease. Techniques will be used to allow rapid detection (by CMV antigenemia test) and characterization of viral interaction with blood cells of patients following BMT. Specific blood cells infected will be identified, the expression of specific viral mRNAs and proteins identified, and these observations correlated with clinical outcomes. These studies may identify characteristics which will predict which patients will remain asymptomatic and which will develop tissue damage from CMV. 2) To characterize the interaction of virus with lung cells obtained (by bronchoalveolar lavage (BAL), Patterns of viral mRNAs and protein expression in BAL cells will be compared with clinical courses of patients following BMT in an effort to identify indicators of current or predictors of future development of CMV interstitial pneumonitis, the most devastating complication of this infection. 3) To determine the role of bone marrow donor in transmitting CMV. Individual.strains of CMV from donor marrow will be identified using molecular techniques and compared to strains causing post-BMT infections in marrow recipients. These studies should clarify the role of the marrow donor, but may also shed light on the relative importance of blood products, marrow donor, and reactivation of endogenous virus from the recipient in causing CMV infection and disease. These studies may predict the success of prophylactic measures (e.g., giving seronegative blood products to seropositive recipients) for future studies. 4) To study the effect of prophylactic measures and early intervention in preventing CMV disease. Randomized studies of chemo-immunoprophylaxis (for seropositive individuals) and blood product manipulation (for seronegative individuals) are proposed. For all such studies laboratory investigations from the first 3 Aims will be correlated with outcomes. Rapid detection of viremia (Aim 1) will be used as a means of identifying early viremia which will then be treated to try to prevent the development of CMV disease. These studies represent a comprehensive approach to defining effective prophylaxis, for defining predictors of CMV disease, and for clarifying the methods of virus transmission. This should lead to improved understanding of virus interaction with the host and to better methods of prevention and early therapy of viral infection.