Analysis of viruses present in urine from patients with interstitial cystitis

Robles, Maria Teresa Sáenz; Cantalupo, Paul G.; Duray, Alexis M.; Freeland, Melissa; Murkowski, Michelle; Bokhoven, Adrie van; Stephens‐Shields, Alisa J.; Pipas, James M.; Imperiale, Michael J.

doi:10.1007/s11262-020-01767-z

Cited by 11 publications

(9 citation statements)

References 23 publications

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“…Yang et al developed an immunoassay cassette with a handheld reader for HIV urine testing in point-of-care diagnostics [ 40 ]. Robles et al analyzed viruses present in urine from patients with interstitial cystitis [ 41 ]. Other viruses in urine described in literature include – Zika virus [ 42 ], hepatitis C [ 43 ], human papiloma virus [ 44 ].…”

Section: Introductionmentioning

confidence: 99%

Review: Detection and quantification of proteins in human urine

Aitekenov

Gaipov

Bukasov

2021

Talanta

124

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Extensive medical research showed that patients, with high protein concentration in urine, have various kinds of kidney diseases, referred to as proteinuria. Urinary protein biomarkers are useful for diagnosis of many health conditions – kidney and cardio vascular diseases, cancers, diabetes, infections. This review focuses on the instrumental quantification (electrophoresis, chromatography, immunoassays, mass spectrometry, fluorescence spectroscopy, the infrared spectroscopy, and Raman spectroscopy) of proteins (the most of all albumin) in human urine matrix. Different techniques provide unique information on what constituents of the urine are. Due to complex nature of urine, a separation step by electrophoresis or chromatography are often used for proteomics study of urine. Mass spectrometry is a powerful tool for the discovery and the analysis of biomarkers in urine, however, costs of the analysis are high, especially for quantitative analysis. Immunoassays, which often come with fluorescence detection, are major qualitative and quantitative tools in clinical analysis. While Infrared and Raman spectroscopies do not give extensive information about urine, they could become important tools for the routine clinical diagnostics of kidney problems, due to rapidness and low-cost. Thus, it is important to review all the applicable techniques and methods related to urine analysis. In this review, a brief overview of each technique’s principle is introduced. Where applicable, research papers about protein determination in urine are summarized with the main figures of merits, such as the limit of detection, the detectable range, recovery and accuracy, when available.

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Section: Introductionmentioning

confidence: 99%

Review: Detection and quantification of proteins in human urine

Aitekenov

Gaipov

Bukasov

2021

Talanta

124

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“…BKPyV and JCPyV are highly prevalent in the population, with most individuals initially getting infected in early childhood and maintaining a lifelong infection thereafter (27,28). The infections of BKPyV, also known as Human polyomavirus 1, are not associated with disease in immunocompetent individuals but can cause nephropathy and allograft failure in individuals receiving a renal transplant (29)(30)(31)(32). In individuals with hemorrhagic cystitis, BKPyV can be found at very high titers in urine (.10 8 copies/ml of urine) (10).…”

mentioning

confidence: 99%

In Vivo Generation of BK and JC Polyomavirus Defective Viral Genomes in Human Urine Samples Associated with Higher Viral Loads

Addetia

Phung

Bradley

et al. 2021

J Virol

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Defective viral genomes (DVGs) are parasitic viral sequences containing point mutations, deletions, or duplications that might interfere with replication. DVGs are often associated with viral passage at high multiplicities of infection in culture systems but have been increasingly reported in clinical specimens. To date however, only RNA viruses have been shown to contain DVGs in clinical specimens. Here, using direct deep sequencing with multiple library preparation strategies and confirmatory ddPCR of urine samples taken from immunosuppressed individuals, we show clinical BKPyV and JCPyV strains contain widespread genomic rearrangements across multiple loci that likely interfere with viral replication. BKPyV DVGs were derived from BKPyV genotypes Ia, Ib-1, and Ic. The presence of DVGs was associated with specimens containing higher viral loads but never reached clonality, consistent with a model of parasitized replication. These DVGs persisted during clinical infection as evidenced in two separate pairs of samples containing BK virus collected from the same individual up to 302 days apart. In a separate individual, we observed the generation of DVGs after a 57.5-fold increase in viral load. In summary, by extending the presence of DVGs in clinical specimens to DNA viruses, we demonstrate the ubiquity of DVGs in clinical virology. IMPORTANCE Defective viral genomes (DVGs) can have a significant impact on the production of infectious virus particles. DVGs have only been identified in cultured viruses passaged at high multiplicities of infection and RNA viruses collected from clinical specimens – no DNA virus in the wild has been shown to contain DVGs. Here, we identified BK and JC polyomavirus DVGs in clinical urine specimens and demonstrated that these DVGs are more frequently identified in samples with higher viral loads. The strains containing DVGs had rearrangements throughout their genomes with the majority affecting genes required for viral replication. Longitudinal analysis showed these DVGs can persist during an infection, but do not reach clonality within the chronically infected host. Our identification of polyomavirus DVGs suggests these parasitic sequences exist across the many classes of viruses capable of causing human disease.

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“…4 A, C). A recent study found evidence of two human polyomavirus infections in IC urine samples; this finding hints at a viral etiology [ 37 ]. Therefore, in the diagnosis of HIC, careful screening for autoimmune diseases and microbial infection-related indicators might be valuable to determine the etiology.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel biomarkers in Hunner’s interstitial cystitis using the CIBERSORT, an algorithm based on machine learning

Wei

Wang

et al. 2021

BMC Urol

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Background Hunner’s interstitial cystitis (HIC) is a complex disorder characterized by pelvic pain, disrupted urine storage, and Hunner lesions seen on cystoscopy. There are few effective diagnostic biomarkers. In the present study, we used the novel machine learning tool CIBERSORT to measure immune cell subset infiltration and potential novel diagnostic biomarkers for HIC. Methods The GSE11783 and GSE57560 datasets were downloaded from the Gene Expression Omnibus for analysis. Ten HIC and six healthy samples from GSE11783 were analyzed using the CIBERSORT algorithm. Gene Set Enrichment Analysis (GSEA) was performed to identify biological processes that occur during HIC pathogenesis. Finally, expression levels of 11 T cell follicular helper cell (Tfh) markers were compared between three healthy individuals and four patients from GSE57560. Results Six types of immune cells in HIC from GSE11783 showed significant differences, including resting mast cells, CD4+ memory-activated T cells (CD3+ CD4+ HLA-DR+ cells), M0 and M2 macrophages, Tfh cells, and activated natural killer cells. Except for plasma cells, there were no significant differences between Hunner’s lesion and non-Hunner’s lesion areas in HIC. The GSEA revealed significantly altered biological processes, including antigen–antibody reactions, autoimmune diseases, and infections of viruses, bacteria, and parasites. There were 11 Tfh cell markers with elevated expression in patients from GSE57560. Conclusion This was the first demonstration of Tfh cells and CD3+ CD4+ HLA-DR+ cells with elevated expression in HIC. These cells might serve as novel diagnostic biomarkers.

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Analysis of viruses present in urine from patients with interstitial cystitis

Cited by 11 publications

References 23 publications

Review: Detection and quantification of proteins in human urine

Review: Detection and quantification of proteins in human urine

In Vivo Generation of BK and JC Polyomavirus Defective Viral Genomes in Human Urine Samples Associated with Higher Viral Loads

Identification of novel biomarkers in Hunner’s interstitial cystitis using the CIBERSORT, an algorithm based on machine learning

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