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ESTABLISHMENT OF A REPLICATION SYSTEM FOR WU POLYOMAVIRUS

吴多瘤病毒复制体系的建立

基本信息

批准号：
8282707
负责人：
DAVID WANG
金额：
$ 19万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2014-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): WU polyomavirus (WUV) is a newly discovered virus that has been widely detected in respiratory secretions of many patients suffering acute respiratory disease. Seroepidemiologic studies have determined that ~90% of adults in the general population have anti-WUV antibodies and thus the vast majority of the world's population has been infected at some point in time by WUV. Currently, the pathogenic potential of WUV is undefined. In some patients with acute respiratory disease, WUV is the only virus detected despite extensive screening for other respiratory viruses, raising the possibility that WUV causes respiratory disease. Based on paradigms provided by the known human pathogens BK and JC polyomaviruses, infection by WUV may result in persistent, lifelong infection that may lead to significant human disease in immunocompromised individuals. In addition, there has long been controversy as to whether SV40, BK and JC viruses play a role in human cancers; the recent discovery of Merkel polyomavirus and its strong association with Merkel cell carcinoma has provided the most compelling link to date between a polyomavirus and cancer. These studies raise the question of whether WUV might be associated with any tumors. Efforts to address these questions, as well as studies aimed at characterizing the fundamental virologic properties of WUV, would be greatly facilitated by the development of a cell culture replication system for WUV. The lack of any culture system for propagation of WUV is currently the fundamental barrier to further characterization of the virus and assessment of its relationship to human disease. For example, fulfillment of Koch's postulates, the gold standard for establishing microbial disease causality, necessarily requires that the agent be grown in culture. In addition, studies of receptors for WUV entry (and thus virus tropism), viral replication mechanisms and detailed analysis of intracellular WUV-host interactions are dependent on having robust culture systems. Successful culture of WUV is a critical milestone that would facilitate many future, long-term experiments essential for understanding of WUV biology.

描述（由申请方提供）：WU多瘤病毒（WUV）是一种新发现的病毒，已在许多急性呼吸道疾病患者的呼吸道分泌物中广泛检出。血清流行病学研究已经确定，一般人群中约90%的成年人具有抗WUV抗体，因此世界上绝大多数人口在某个时间点被WUV感染。目前，WUV的致病潜力尚未确定。在一些急性呼吸道疾病患者中，尽管对其他呼吸道病毒进行了广泛的筛查，但WUV是唯一检测到的病毒，这增加了WUV引起呼吸道疾病的可能性。基于已知的人类病原体BK和JC多瘤病毒提供的范例，WUV感染可能导致持续的终身感染，这可能导致免疫功能低下个体的重大人类疾病。此外，关于SV 40、BK和JC病毒是否在人类癌症中发挥作用一直存在争议;最近发现的默克尔多瘤病毒及其与默克尔细胞癌的密切联系提供了迄今为止多瘤病毒与癌症之间最令人信服的联系。这些研究提出了WUV是否可能与任何肿瘤相关的问题。努力解决这些问题，以及旨在表征WUV的基本病毒学特性的研究，将大大促进WUV的细胞培养复制系统的发展。缺乏任何用于WUV繁殖的培养系统是目前进一步表征该病毒和评估其与人类疾病关系的根本障碍。例如，实现科赫假设，建立微生物疾病因果关系的黄金标准，必然要求病原体在培养物中生长。此外，WUV进入受体的研究（因此病毒嗜性），病毒复制机制和细胞内WUV-宿主相互作用的详细分析依赖于具有强大的培养系统。WUV的成功培养是一个重要的里程碑，将促进许多未来的长期实验，这对于了解WUV生物学至关重要。