Computer Simulation of Epstein Barr Virus Infection

EB 病毒感染的计算机模拟

• 批准号: 6852834
• 负责人: David A. Thorley-Lawson
• 金额: $ 46.13万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6852834
• 关键词: B lymphocyte; Epstein Barr virus; T lymphocyte; clinical research; computer simulation; computer system design /evaluation; human tissue; immunologic techniques; mononucleosis; neutralizing antibody; polymerase chain reaction; supercomputer; virus infection mechanism

DESCRIPTION (provided by applicant): Epstein-Barr vires persistently infects >95% of the adult human population. It causes infectious mononucleosis and is associated with several important human cancers. Considerable progress has been made recently in understanding how EBV establishes and maintains persistent infection. It is apparent that EBV uses various combinations of latent gene expression patterns to manipulate the biology of normal B lymphocytes. This allows EBV to establish latent persistent infection in resting memory B cells in the blood and replicate in plasma cells in the lymphoepithelium of Waldeyer's ring (tonsils and adenoids). However, these studies have all been static and an understanding of the dynamics of the infection is lacking. In the absence of a suitable animal model, we propose to develop a new generation of computer simulation. The application of supercomputing on distributed clusters of processors will allow us to develop an unprecedented level of sophistication and complexity. We will employ an agent-based approach, which makes it possible to represent the actual anatomy of the relevant tissues and organs and the dynamic changes that occur over time and space. These features are not possible with traditional mathematical models based on ordinary differential equations. A simulation involving approximately 108 agents is within reach and should produce realistic results, based on previous experience with similar simulations of traffic and wireless communication systems. We will use sensitive PCR and immunological techniques to accurately measure levels of virus shedding, virus infected cells, EBV specific CD4 and CD8 cells and neutralizing antibody as acute infection resolves into persistent infection. The data will then be used to inform the computer simulation. This approach will allow us to define the infection parameters necessary to predict the observed kinetics of infection. Ultimately, the simulation will be used to test the effects of perturbations such as lowering the numbers of T cells (immunosuppression) eliminating infectious virus (anti-viral and/or vaccines) and to ask if complete clearance (i.e. cure) of the virus is realistic or even possible.

描述（由申请人提供）：Epstein-Barr Vires持续感染> 95％的成年人人口。它会引起传染性单核细胞增多症，并与几种重要的人类癌症有关。最近在理解EBV如何建立和保持持续感染方面取得了长足进展。显然，EBV使用潜在基因表达模式的各种组合来操纵正常B淋巴细胞的生物学。这使EBV可以在血液中的静息记忆B细胞中建立潜在的持续感染，并在Waldeyer环（扁桃体和腺样体）的淋巴上皮中复制。但是，这些研究都是静态的，并且缺乏对感染动力学的理解。在没有合适的动物模型的情况下，我们建议开发新一代的计算机模拟。超级计算在处理器的分布式簇上的应用将使我们能够发展出前所未有的复杂性和复杂性。我们将采用一种基于代理的方法，这使得可以代表相关组织和器官的实际解剖结构以及随时间和空间的动态变化。基于普通微分方程的传统数学模型无法使用这些功能。涉及大约108个代理的模拟可以触及，并应基于以前的交通和无线通信系统模拟的经验而产生现实的结果。我们将使用敏感的PCR和免疫学技术来准确测量病毒脱落的水平，感染病毒感染细胞，EBV特异性CD4和CD8细胞，并将抗体中和抗体作为急性感染解决了持续感染。然后，数据将用于告知计算机模拟。这种方法将使我们能够定义预测观察到的感染动力学所需的感染参数。最终，该模拟将用于测试扰动的影响，例如消除T细胞的数量（免疫抑制）消除传染性病毒（抗病毒和/或疫苗），并询问该病毒的完全清除率（即治愈）是否现实甚至可能是现实的甚至可能。