title: Replication of oral BK virus in human salivary gland cells.
abstract: BK polyomavirus (BKPyV) is the most common viral pathogen among allograft patients. Increasing evidence links BKPyV to the human oral compartment and to HIV-associated salivary gland disease (HIVSGD). To date, few studies have analyzed orally derived BKPyV. This study aimed to characterize BKPyV isolated from throat wash (TW) samples from HIVSGD patients. The replication potential of HIVSGD-derived clinical isolates HIVSGD-1 and HIVSGD-2, both containing the noncoding control region (NCCR) architecture OPQPQQS, were assessed and compared to urine-derived virus. The BKPyV isolates displayed significant variation in replication potential. Whole-genome alignment of the two isolates revealed three nucleotide differences that were analyzed for a potential effect on the viral life cycle. Analysis revealed a negligible difference in NCCR promoter activity despite sequence variation and emphasized the importance of functional T antigen (Tag) for efficient replication. HIVSGD-1 encoded full-length Tag, underwent productive infection in both human salivary gland cells and kidney cells, and expressed viral DNA and Tag protein. Additionally, HIVSGD-1 generated DNase-resistant particles and by far surpassed the replication potential of the kidney-derived isolate in HSG cells. HIVSGD-2 encoded a truncated form of Tag and replicated much less efficiently. Quantitation of infectious virus, via the fluorescent forming unit assay, suggested that HIVSGD BKPyV had preferential tropism for salivary gland cells over kidney cells. Similarly, the results suggested that kidney-derived virus had preferential tropism for kidney cells over salivary gland cells. Evidence of HIVSGD-derived BKPyV oral tropism and adept viral replication in human salivary gland cells corroborated the potential link between HIVSGD pathogenesis and BKPyV.
authors.affiliation: Microbiology and Immunology Department, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Raquel
authors.initials: R
authors.lastname: Burger-Calderon
authors.forename: Victoria
authors.initials: V
authors.lastname: Madden
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Hallett
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Gingerich
authors.forename: Volker
authors.initials: V
authors.lastname: Nickeleit
authors.forename: Jennifer
authors.initials: J
authors.lastname: Webster-Cyriaque
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001739:BK Virus / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D015139:Blotting, Southern; D002522:Chlorocebus aethiops; D017931:DNA Primers; D004279:DNA, Viral / Q000235:genetics; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012469:Salivary Glands / Q000166:cytology / Q000821:virology*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014709:Vero Cells; D014779:Virus Replication
chemical_list: D017931:DNA Primers; D004279:DNA, Viral