The BK virus and HIV-associated salivary gland disease: corroborating the link

BK polyomavirus (BKPyV) is the most common viral pathogen among allograft patients and is known to adversely affect immune suppressed individuals since the discovery of the virus in 1971. Increasing evidence links BKPyV to the human oral compartment and to HIV-associated salivary gland disease (HIVSGD). To date, few studies have analyzed oral-derived BKPyV. The studies described in this manuscript, aimed to characterize BKPyV isolated from throatwash (TW) samples of HIVSGD patients. The BKPyV non-coding control region (NCCR) is the main determinant of viral replication and rearranges readily in vivo and in vitro. Further, NCCR rearrangements have been associated with functional differences. This study analyzed 36 clinical samples, of which 29 were BKPyV positive. One hundred percent of TW samples from HIVSGD patients and urine samples from transplant patients yielded BKPyV NCCR sequences. Importantly, 94% of the BKPyV HIVSGD NCCRs carried the rearranged OPQPQQS block arrangement, suggesting a distinctive architecture among this sample set. Of interest, in the 22% of BKPyV positive oral samples from individuals without HIVSGD, the BKPyV substrains were distinct from OPQPQQS. The studies also assessed the replication potential and NCCR promoter strength of HIVSGD-derived clinical isolates in vitro. The majority of HIVSGD-derived BKPyV isolates underwent productive infection and had active promoters in an oral cell culture system. Quantitation of infectious virus suggested that HIVSGD BKPyV had preferential tropism for salivary gland cells over kidney 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.Doctor of Philosoph