title: First detection and complete genome sequence of a phylogenetically distinct human polyomavirus 6 highly prevalent in human bile samples.
abstract: Oncovirus-associated malignancies are potentially preventable diseases with major public health significance. Human polyomaviruses (HPyVs) may be associated with oncogenesis or symptomatic illnesses in immunocompromised patients, but the site of viral shedding of most recently discovered HPyVs remains obscure. Using real-time PCR assay using specific primers targeting the HPyV6 large tumor antigen gene, we detected a phylogenetically distinct HPyV6 which was highly prevalent in the bile samples of patients with malignant biliary obstruction (18.8%) and acute gallstone cholangitis (5.5%). The prevalence rate and mean viral load of this HPyV6 were highest in the cholangiocarcinoma subgroup (27.6% and 2.41 × 104copies/ml). These findings were confirmed with another real-time PCR assay using specific primers targeting the HPyV6 viral capsid protein 2 gene. These bile HPyV6 strains may represent a novel clade of HPyV6 as they formed a distinct cluster from the other HPyV6s and exhibited >2% differences in amino acid sequences in their major proteins. While HPyV6 was unlikely the cause of the patients' acute symptoms and liver dysfunction, the virus may be related to immunosuppression in patients with malignancy and/or important in the oncogenesis of cholangiocarcinoma in patients without coinfection with other oncogenic microbes. Further studies to ascertain a causative role of HPyV6 in cholangiocarcinoma should be conducted.
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong; Department of Microbiology, The University of Hong Kong, Hong Kong; Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong; Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong. Electronic address: jfwchan@hku.hk.
authors.forename: Jasper F W
authors.initials: JF
authors.lastname: Chan
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong.
authors.forename: Kah-Meng
authors.initials: KM
authors.lastname: Tee
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong.
authors.forename: Garnet K Y
authors.initials: GK
authors.lastname: Choi
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong.
authors.forename: Rosana W S
authors.initials: RW
authors.lastname: Poon
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong.
authors.forename: Kevin T P
authors.initials: KT
authors.lastname: Ng
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong.
authors.forename: Kwok-Hung
authors.initials: KH
authors.lastname: Chan
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Ivan F N
authors.initials: IF
authors.lastname: Hung
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong.
authors.forename: Kwan
authors.initials: K
authors.lastname: Man
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong; Department of Microbiology, The University of Hong Kong, Hong Kong; Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong; Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong; The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong. Electronic address: kyyuen@hku.hk.
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001646:Bile / Q000821:virology*; D018281:Cholangiocarcinoma / Q000821:virology; D002761:Cholangitis / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D016679:Genome, Viral; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016867:Immunocompromised Host; D008107:Liver Diseases / Q000453:epidemiology / Q000821:virology; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D011120:Polyomavirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*; D027601:Polyomavirus Infections / Q000453:epidemiology / Q000821:virology*; D015995:Prevalence; D060888:Real-Time Polymerase Chain Reaction; D019562:Viral Load; D055815:Young Adult
chemical_list: D004279:DNA, Viral
keywords: Bile; Biliary; Cancer; Carcinoma; Cholangiocarcinoma; Cholangitis; HPyV6; Malignancy; Polyomavirus