Successful treatment of hemorrhagic cystitis after hematopoietic stem cell transplantation with intravesical hyaluronic acid

Işık, Pamir; Özbek, Namık; Azık, Fatih Mehmet; Bilir, Özlem; Baylan, Burhan; Tunç, Bahattin

doi:10.1111/petr.12354

Cited by 5 publications

(3 citation statements)

References 6 publications

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“…Our observations provide structural clues about GAG binding to BKV and may form a basis to determine the precise molecular mechanism of GAG interaction using shorter, defined fragments of heparin, which may be more amenable to high-resolution structural characterization. Interestingly GAG analogs have reportedly been used to treat BKV-associated disease ( Van der Aa et al., 2014 , Winter et al., 2015 , Isik et al., 2014 , Cervigni, 2015 ). The rationale for such treatments was based on restoration of the barrier function of the bladder epithelium, but in light of recent results (including those presented here), it is possible that GAGs may bind directly to BKV and perturb cellular attachment or entry.…”

Section: Discussionmentioning

confidence: 99%

The Structure of an Infectious Human Polyomavirus and Its Interactions with Cellular Receptors

et al. 2018

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SummaryBK polyomavirus (BKV) causes polyomavirus-associated nephropathy and hemorrhagic cystitis in immunosuppressed patients. These are diseases for which we currently have limited treatment options, but potential therapies could include pre-transplant vaccination with a multivalent BKV vaccine or therapeutics which inhibit capsid assembly or block attachment and entry into target cells. A useful tool in such efforts would be a high-resolution structure of the infectious BKV virion and how this interacts with its full repertoire of cellular receptors. We present the 3.4-Å cryoelectron microscopy structure of native, infectious BKV in complex with the receptor fragment of GT1b ganglioside. We also present structural evidence that BKV can utilize glycosaminoglycans as attachment receptors. This work highlights features that underpin capsid stability and provides a platform for rational design and development of urgently needed pharmacological interventions for BKV-associated diseases.

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Section: Discussionmentioning

confidence: 99%

The Structure of an Infectious Human Polyomavirus and Its Interactions with Cellular Receptors

et al. 2018

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“…GAGs have also been investigated as possible treatments for BKV-induced hemorrhagic cystitis following bone marrow transplant (Arthur et al, 1986; Reploeg et al, 2001) and for a potentially BKV/JCV-associated chronic bladder syndrome known as interstitial cystitis (Van der Aa et al, 2014; Winter et al, 2015). GAGs and GAG analogs, such as pentosan polysulfate, heparin, and chondroitin sulfate, are currently recommended treatments for interstitial cystitis (Al-Zahrani and Gajewski, 2011; Cervigni, 2015; Madersbacher et al, 2013; Parsons and Mulholland, 1987; Tutolo et al, 2016), and there is also evidence that treatment with hyaluronic acid (a non-sulfated GAG) can relieve symptoms and achieve remission of hemorrhagic cystitis (Iavazzo et al, 2007; Isik et al, 2014; Miodosky et al, 2006; Shao et al, 2012). Although previous justifications for these treatments have focused on GAGs restoring the barrier function of the bladder epithelium, it is possible to imagine that treatment with GAGs or GAG analogs may actually be inhibiting polyomavirus infectious entry.…”

Section: Discussionmentioning

confidence: 99%

Infectious Entry and Neutralization of Pathogenic JC Polyomaviruses

et al. 2017

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Summary Progressive multifocal leukoencephalopathy (PML) is a lethal brain disease caused by uncontrolled replication of JC polyomavirus (JCV). JCV strains recovered from the brains of PML patients carry mutations that prevent the engagement of sialylated glycans, which are thought to serve as receptors for the infectious entry of wild-type JCV. In this report, we show that non-sialylated glycosaminoglycans (GAGs) can serve as alternative attachment receptors for the infectious entry of both wild-type and PML-mutant JCV strains. After GAG-mediated attachment, PML-mutant strains engage non-sialylated non-GAG co-receptor glycans, such as asialo-GM1. JCV-neutralizing monoclonal antibodies isolated from patients who recovered from PML appear to block infection by preventing the docking of post-attachment co-receptor glycans in an apical pocket of the JCV major capsid protein. Identification of the GAG-dependent/sialylated glycan-independent alternative entry pathway should facilitate the development of infection inhibitors, including recombinant neutralizing antibodies.

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“…GAGs have also been investigated as possible treatments for BKV-induced hemorrhagic cystitis following bone marrow transplant (Arthur et al, 1986;Reploeg et al, 2001) and for a potentially BKV/JCV-associated chronic bladder syndrome known as interstitial cystitis (Van der Aa et al, 2014;Winter et al, 2015). GAGs and GAG analogs, such as pentosan polysulfate, heparin, and chondroitin sulfate, are currently recommended treatments for interstitial cystitis (Al-Zahrani and Gajewski, 2011;Cervigni, 2015;Madersbacher et al, 2013;Parsons and Mulholland, 1987;Tutolo et al, 2016), and there is also evidence that treatment with hyaluronic acid (a non-sulfated GAG) can relieve symptoms and achieve remission of hemorrhagic cystitis (Iavazzo et al, 2007;Isik et al, 2014;Miodosky et al, 2006;Shao et al, 2012). Although previous justifications for these treatments have focused on GAGs restoring the barrier function of the bladder epithelium, it is possible to imagine that treatment with GAGs or GAG analogs may actually be inhibiting polyomavirus infectious entry.…”

Section: Discussionmentioning

confidence: 99%