title: Survey for human polyomaviruses in cancer.
abstract: Over the past 8 years, the discovery of 11 new human polyomaviruses (HPyVs) has revived interest in this DNA tumor virus family. Although HPyV infection is widespread and largely asymptomatic, one of these HPyVs, Merkel cell polyomavirus (MCV), is a bona fide human tumor virus. JC virus (JCV), BK virus, HPyV7, and trichodysplasia-spinulosa virus (TSV) can cause nonneoplastic diseases in the setting of immunosuppression. Few specific reagents are available to study the biology of the newly discovered HPyVs. We developed a pan-HPyV-screening method using a cocktail of 3 antibodies that, when combined, recognize T antigen proteins of all HPyVs. We validated detection characteristics of the antibody cocktail by immunoblotting and immunohistochemistry and screened 1,184 cases, including well-defined diseases and tumor tissue microarrays. This assay robustly detected MCV, TSV, JCV, and HPyV7 in etiologically related diseases. We further identified WU polyomavirus in a case of chronic lymphocytic lymphoma-associated bronchitis. Except for scattered, incidentally infected cells in 5% of lung squamous cell carcinomas and colon adenocarcinomas, a broad panel of tumor tissues was largely negative for infection by any HPyV. This method eliminates known HPyVs as suspected causes of cancers investigated in this study. Pan-HPyV survey can be applied to identify diseases associated with recently discovered polyomaviruses.
authors.affiliation: Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: Tuna
authors.initials: T
authors.lastname: Toptan
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Yousem
authors.affiliation: Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Jonhan
authors.initials: J
authors.lastname: Ho
authors.affiliation: Division of Virology, Kawasaki City Institute for Public Health, Kanagawa, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsushima
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Laura P
authors.initials: LP
authors.lastname: Stabile
authors.affiliation: Department of Pathology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Maria-Teresa
authors.initials: MT
authors.lastname: Fernández-Figueras
authors.affiliation: Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Bhargava
authors.affiliation: Department of Microbiology, Yokohama City University School of Medicine, Kanagawa, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Ryo
authors.affiliation: Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Moore
authors.affiliation: Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chang