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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI095922-02
Application #
8282707
Study Section
Virology - A Study Section (VIRA)
Program Officer
Park, Eun-Chung
Project Start
2011-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2012
Total Cost
$190,000
Indirect Cost
$65,000
Name
Washington University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Siebrasse, Erica A; Nguyen, Nang L; Smith, Colin et al. (2014) Immunohistochemical detection of KI polyomavirus in lung and spleen. Virology 468-470:178-84