CYTOMEGALOVIRUS INFECTION FOLLOWING BONE MARROW TRANSPLANTATION

巨细胞病毒（CMV）感染已成为最常见的感染原因 骨髓移植（BMT）后死亡。 防止 这种感染引起的疾病需要了解CMV是如何 获得性感染，因为有些患者会重新激活潜伏感染，而另一些患者则会 从外源性来源（特别是血液制品）获得感染 或者是之前接触过巨细胞病毒的捐献者的骨髓 长期 当前提案的目标是澄清CMV 感染发生时，寻找可以区分当前感染的实验室标记物， (or预测CMV疾病的发展），以及 最终改善CMV疾病和感染的预防和治疗 BMT后的患者。 为此，以下具体目标和 本文拟开展以下研究：1）明确病毒血症在预测CMV中的作用 疾病 将使用快速检测技术（通过CMV 抗原血症试验）和病毒与血液相互作用的表征 BMT后患者的细胞。 感染的特定血细胞会 鉴定，特异性病毒mRNA和蛋白质的表达， 并且这些观察结果与临床结果相关。 这些研究 可以识别出预测哪些患者将留在 无症状并且将由CMV引起组织损伤。2)到 表征病毒与获得的肺细胞的相互作用（通过 支气管肺泡灌洗（BAL），病毒mRNA和蛋白的模式 将BAL细胞中的表达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 CMV间质性肺炎的未来发展，最具破坏性的 这种感染的并发症。3)为了确定骨髓的作用 供体传播CMV。 来自供体骨髓的CMV个体菌株 将使用分子技术进行鉴定， 导致骨髓移植后感染。 这些研究应 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 在引起CMV感染和疾病中，来自受体的内源性病毒。 这些研究可以预测预防措施的成功（例如， 将血清反应阴性的血液制品给予血清反应阳性的受者） 问题研究4)探讨预防措施的效果， 预防CMV疾病。 随机研究 化学免疫预防（针对血清反应阳性个体）和血液制品 操作（用于血清阴性个体）。 所有此类 将前3个目标的实验室研究与 有结果。 将使用快速检测病毒血症（目标1）作为一种手段 发现早期病毒血症，然后进行治疗， CMV疾病的发展。 这些研究代表了一个全面的 定义有效预防的方法，用于定义CMV的预测因子 疾病，并澄清病毒传播的方法。 这应该 提高对病毒与宿主相互作用的认识， 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.