scholarly journals Fate of the Urinary Tract Virus BK Human Polyomavirus in Source-Separated Urine

2018 ◽  
Vol 84 (7) ◽  
Author(s):  
Heather E. Goetsch ◽  
Linbo Zhao ◽  
Mariah Gnegy ◽  
Michael J. Imperiale ◽  
Nancy G. Love ◽  
...  

ABSTRACTHuman polyomaviruses are emerging pathogens that infect a large percentage of the human population and are excreted in urine. Consequently, urine that is collected for fertilizer production often has high concentrations of polyomavirus genes. We studied the fate of infectious double-stranded DNA (dsDNA) BK human polyomavirus (BKPyV) in hydrolyzed source-separated urine with infectivity assays and quantitative PCR (qPCR). Although BKPyV genomes persisted in the hydrolyzed urine for long periods of time (T90[time required for 90% reduction in infectivity or gene copies] of >3 weeks), the viruses were rapidly inactivated (T90of 1.1 to 11 h) in most of the tested urine samples. Interestingly, the infectivity of dsDNA bacteriophage surrogate T3 (T90of 24 to 46 days) was much more persistent than that of BKPyV, highlighting a major shortcoming of using bacteriophages as human virus surrogates. Pasteurization and filtration experiments suggest that BKPyV virus inactivation was due to microorganism activity in the source-separated urine, and SDS-PAGE Western blots showed that BKPyV protein capsid disassembly is concurrent with inactivation. Our results imply that stored urine does not pose a substantial risk of BKPyV transmission, that qPCR and infectivity of the dsDNA surrogate do not accurately depict BKPyV fate, and that microbial inactivation is driven by structural elements of the BKPyV capsid.IMPORTANCEWe demonstrate that a common urinary tract virus has a high susceptibility to the conditions in hydrolyzed urine and consequently would not be a substantial exposure route to humans using urine-derived fertilizers. The results have significant implications for understanding virus fate. First, by demonstrating that the dsDNA (double-stranded DNA) genome of the polyomavirus lasts for weeks despite infectivity lasting for hours to days, our work highlights the shortcomings of using qPCR to estimate risks from unculturable viruses. Second, commonly used dsDNA surrogate viruses survived for weeks under the same conditions that BK polyomavirus survived for only hours, highlighting issues with using virus surrogates to predict how human viruses will behave in the environment. Finally, our mechanistic inactivation analysis provides strong evidence that microbial activity drives rapid virus inactivation, likely through capsid disassembly. Overall, our work underlines how subtle structural differences between viruses can greatly impact their environmental fate.

mBio ◽  
2011 ◽  
Vol 2 (5) ◽  
Author(s):  
Paul G. Cantalupo ◽  
Byron Calgua ◽  
Guoyan Zhao ◽  
Ayalkibet Hundesa ◽  
Adam D. Wier ◽  
...  

ABSTRACTAt this time, about 3,000 different viruses are recognized, but metagenomic studies suggest that these viruses are a small fraction of the viruses that exist in nature. We have explored viral diversity by deep sequencing nucleic acids obtained from virion populations enriched from raw sewage. We identified 234 known viruses, including 17 that infect humans. Plant, insect, and algal viruses as well as bacteriophages were also present. These viruses represented 26 taxonomic families and included viruses with single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), positive-sense ssRNA [ssRNA(+)], and dsRNA genomes. Novel viruses that could be placed in specific taxa represented 51 different families, making untreated wastewater the most diverse viral metagenome (genetic material recovered directly from environmental samples) examined thus far. However, the vast majority of sequence reads bore little or no sequence relation to known viruses and thus could not be placed into specific taxa. These results show that the vast majority of the viruses on Earth have not yet been characterized. Untreated wastewater provides a rich matrix for identifying novel viruses and for studying virus diversity.IMPORTANCEAt this time, virology is focused on the study of a relatively small number of viral species. Specific viruses are studied either because they are easily propagated in the laboratory or because they are associated with disease. The lack of knowledge of the size and characteristics of the viral universe and the diversity of viral genomes is a roadblock to understanding important issues, such as the origin of emerging pathogens and the extent of gene exchange among viruses. Untreated wastewater is an ideal system for assessing viral diversity because virion populations from large numbers of individuals are deposited and because raw sewage itself provides a rich environment for the growth of diverse host species and thus their viruses. These studies suggest that the viral universe is far more vast and diverse than previously suspected.


2019 ◽  
Author(s):  
John Lafleur ◽  
Richard L. Amdur

AbstractParaoxonases are mammalian enzymes that have a number of roles including the inhibition of bacterial virulence and biofilm formation by microorganisms that quorum sense with acylated homoserine lactones. Paraoxonases have previously been reported to inhibit P. aeruginosa biofilm formation in mammalian airways and skin. An innate immune role for paraoxonases in urinary tract infection has not previously been reported. We performed western blots for paraoxonase1 in urine from patients with urinary tract infection; we also tested urinary tract infection urine for the presence of acylated homoserine lactones using a cellular reporter system. We report here that paraoxonase1 was not found with our western blot assay in the urine of normal control patients; in those with urinary tract infection, paraoxonase1 was associated with E. coli UTI. Acylated homoserine lactones, but not paraoxonases, were found in the bulk urine of those with P. aeruginosa urinary tract infection. We hypothesize that paraoxonase may play a similar innate immune role in infected urine as has previously described in skin and airways.


2005 ◽  
Vol 129 (1) ◽  
pp. 69-73 ◽  
Author(s):  
Renzo Boldorini ◽  
Claudia Veggiani ◽  
Diana Barco ◽  
Guido Monga

Abstract Context.—Distinct human polyomavirus genotypes cause different diseases in patients with renal transplants: BK virus (BKV) causes tubulointerstitial nephritis and ureteral stenosis, whereas both JC virus (JCV) and BKV are responsible for hemorrhagic cystitis. These findings could result from a selective infection of kidney and urinary tract segments by JCV or BKV. Objective.—To verify this hypothesis, 10 complete, unselected, consecutive autopsies from 9 immunocompetent patients and 1 patient affected by acquired immunodeficiency syndrome were investigated. Design.—Samples from kidneys (n = 80), renal pelvis (n = 20), ureter (n = 40), and urinary bladder (n = 30) obtained from 10 consecutive autopsies were investigated by means of multiplex nested polymerase chain reaction to detect polyomavirus DNA and to distinguish different species of the Polyomavirus genus. In situ hybridization and immunohistochemistry were also carried out to define the viral status of the infected tissues. Results.—Polyomavirus DNA was detected in all of the subjects (positive samples ranging from 2 to 7 samples), for a total of 43 of 170 samples (25.3%), distributed as follows: urinary bladder (10/30, 33%), renal pelvis (6/20, 30%), ureter (10/40, 25%), and kidney tissue (17/80, 21%). We found that JCV was most frequently detected overall (23/43 samples, 53.5%) and was also detected most frequently within the kidney (8/17 positive samples, 47%), the renal pelvis (5/6 positive samples, 70%), and the ureter (7/10 positive samples, 70%), whereas BKV was found in 14 samples (32.5%), and it was the prevailing genotype in urinary bladder (6/10 positive samples, 60%). Coinfection of BKV-JCV was found in 6 samples (14%). Immunohistochemistry and in situ hybridization returned negative results. Conclusions.—The viruses JCV and BKV latently persist randomly in kidney and urinary tract. Distinct diseases induced by them could be related more closely to molecular viral rearrangements than to the topographic distribution of latent viruses.


2014 ◽  
Vol 89 (1) ◽  
pp. 857-862 ◽  
Author(s):  
Christian Berrios ◽  
Joonil Jung ◽  
Blake Primi ◽  
Michael Wang ◽  
Chandrasekhar Pedamallu ◽  
...  

Malawi polyomavirus (MWPyV) is a recently identified human polyomavirus. Serology for MWPyV VP1 indicates that infection frequently occurs in childhood and reaches a prevalence of 75% in adults. The MWPyV small T antigen (ST) binds protein phosphatase 2A (PP2A), and the large T antigen (LT) binds pRb, p107, p130, and p53. However, the MWPyV LT was less stable than the simian virus 40 (SV40) LT and was unable to promote the growth of normal cells. This report confirms that MWPyV is a widespread human virus expressing T antigens with low transforming potential.


PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246266
Author(s):  
Samuel Thomas ◽  
Christopher D. Dunn ◽  
Lewis J. Campbell ◽  
Douglas W. Strand ◽  
Chad M. Vezina ◽  
...  

Male lower urinary tract symptoms (LUTS) comprise a common syndrome of aging that negatively impacts quality of life. The etiology of LUTS is multifactorial, involving benign prostatic hyperplasia, smooth muscle and neurologic dysfunction, inflammation, sexually transmitted infections, fibrosis, and potentially dysbiosis, but this aspect remains poorly explored. We investigated whether the presence of infectious agents in urine might be associated with LUTS by combining next-generation DNA sequencing for virus discovery, microbiome analysis for characterization of bacterial communities, and mass spectrometry-based metabolomics. In urine from 29 LUTS cases and 9 controls from Wisconsin, we found a statistically significant association between a diagnosis of LUTS and the presence of JC virus (JCV), a common neurotropic human polyomavirus (Polyomaviridae, Betapolyomavirus) linked to severe neurologic disease in rare cases. This association (based on metagenomics) was not borne out when specific polymerase chain reaction (PCR) testing was applied to this set of samples, likely due to the greater sensitivity of PCR. Interestingly, urine metabolomics analysis identified dysregulation of metabolites associated with key LUTS processes. Microbiome analysis found no evidence of microbial community dysbiosis in LUTS cases, but JCV-positive samples contained more Anaerococcus species, which are involved in polymicrobial infections of the urinary tract. Neither age nor body mass index were significantly associated with the presence of urinary JCV—in the initial group or in an additional, regionally distinct group. These data provide preliminary support the hypothesis that viruses such as JCV may play a role in the development or progression of LUTS, together with other infectious agents and host metabolic responses.


2005 ◽  
Vol 79 (22) ◽  
pp. 14244-14252 ◽  
Author(s):  
C. David Lytle ◽  
Jose-Luis Sagripanti

ABSTRACT UV radiation from the sun is the primary germicide in the environment. The goal of this study was to estimate inactivation of viruses by solar exposure. We reviewed published reports on 254-nm UV inactivation and tabulated the sensitivities of a wide variety of viruses, including those with double-stranded DNA, single-stranded DNA, double-stranded RNA, or single-stranded RNA genomes. We calculated D 37 values (fluence producing on average one lethal hit per virion and reducing viable virus to 37%) from all available data. We defined “size-normalized sensitivity” (SnS) by multiplying UV254 sensitivities (D 37 values) by the genome size, and SnS values were relatively constant for viruses with similar genetic composition. In addition, SnS values were similar for complete virions and their defective particles, even when the corresponding D 37 values were significantly different. We used SnS to estimate the UV254 sensitivities of viruses for which the genome composition and size were known but no UV inactivation data were available, including smallpox virus, Ebola, Marburg, Crimean-Congo, Junin, and other hemorrhagic viruses, and Venezuelan equine encephalitis and other encephalitis viruses. We compiled available data on virus inactivation as a function of wavelength and calculated a composite action spectrum that allowed extrapolation from the 254-nm data to solar UV. We combined our estimates of virus sensitivity with solar measurements at different geographical locations to predict virus inactivation. Our predictions agreed with the available experimental data. This work should be a useful step to understanding and eventually predicting the survival of viruses after their release in the environment.


1999 ◽  
Vol 67 (12) ◽  
pp. 6683-6687 ◽  
Author(s):  
David E. Johnson ◽  
Farah K. Bahrani ◽  
C. Virginia Lockatell ◽  
Cinthia B. Drachenberg ◽  
J. Richard Hebel ◽  
...  

ABSTRACT We tested the hypothesis that experimental Proteus mirabilis urinary tract infection in mice would protect against homologous bladder rechallenge. Despite production of serum immunoglobulin G (IgG) and IgM (median titers of 1:320 and 1:80, respectively), vaccinated (infected and antibiotic-cured) mice did not show a decrease in mortality upon rechallenge; the survivors experienced only modest protection from infection (mean log10 number of CFU of P. mirabilisNalr HI4320 per milliliter or gram in vaccinated mice versus sham-vaccinated mice: urine, 100-fold less [3.5 versus 5.5;P = 0.13]; bladder, 100-fold less [3.1 versus 5.1;P = 0.066]; kidneys, 40-fold less [2.7 versus 4.3;P = 0.016]). Western blots using protein from the wild-type strain and isogenic mutants demonstrated antibody responses to MR/P and PMF fimbriae and flagella. There was no correlation between serum IgG or IgM levels and protection from mortality or infection. There was a trend toward elevated serum IgA titers and protection from subsequent challenge (P ≥ 0.09), although only a few mice developed significant serum IgA levels. We conclude that prior infection with P. mirabilis does not protect significantly against homologous challenge.


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