ESTABLISHMENT OF A REPLICATION SYSTEM FOR WU POLYOMAVIRUS

描述（申请人提供）：WU多瘤病毒（WUV）是一种新发现的病毒，广泛存在于许多急性呼吸道疾病患者的呼吸道分泌物中。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感染过WUV。目前，WUV的致病潜力尚不明确。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。根据已知的人类病原体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，可能导致免疫功能低下个体的重大人类疾病。此外，SV40、BK和JC病毒是否在人类癌症中发挥作用一直存在争议；最近发现的梅克尔多瘤病毒及其与梅克尔细胞癌的密切联系为多瘤病毒与癌症之间提供了迄今为止最令人信服的联系。这些研究提出了WUV是否与任何肿瘤相关的问题。解决这些问题的努力，以及旨在表征WUV基本病毒学特性的研究，将极大地促进WUV细胞培养复制系统的发展。目前，缺乏任何用于繁殖WUV的培养系统是进一步表征该病毒并评估其与人类疾病关系的根本障碍。例如，要实现科赫的假设，即确立微生物疾病因果关系的黄金标准，就必须在培养基中培养病原体。此外，研究WUV进入受体（以及病毒的趋向性）、病毒复制机制和细胞内WUV-宿主相互作用的详细分析都依赖于强大的培养系统。WUV的成功培养是一个重要的里程碑，它将促进许多未来的长期实验，这对理解WUV生物学至关重要。

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. PUBLIC HEALTH RELEVANCE: WU polyomavirus is a newly identified virus present in many patients with acute respiratory disease. This proposal aims to develop an in vitro cell culture system for WU polyomavirus in order to better understand its potential role in human diseases.