Bk Virus as Cause of Haemorrhagic Cystitis After Bone Marrow Transplantation

Rice, S J; Bishop, J A; Apperley, J.F.; Gardner, S. D.

doi:10.1016/s0140-6736(85)90843-8

Cited by 38 publications

(16 citation statements)

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“…BKV viruria in renal transplant recipients ranges between 10 to 60% and has been associated with ureteric stenosis (16) and BK viral nephropathy characterized by tubular necrosis and interstitial nephritis (32, 33). In bone marrow transplant recipients, BKV has been linked to hemorrhagic cystitis (13,26,34).Characterization of genetic diversity of BK virus has biologic as well as clinical implications. This information is needed to seek potential relationships between viral genotype and clinical disease.…”

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confidence: 99%

Phylogenetic Analysis of Polyomavirus BK Sequences

Sharma

Gupta

Vats

et al. 2006

J Virol

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Polyomavirus BK (BKV) has emerged as an important pathogen in kidney transplant patients. Existing taxonomic classifications of BKV come from conventional DNA sequence alignments based on limited data derived from the VP1 gene. We have used a phylogenetic whole-genome approach to examine the pattern of diversity and evolutionary relationships between 45 BKV strains isolated from multiple clinical settings. This analysis supports the classification of BKV into six genotypes, of which types V and VI have not been previously recognized. BKV strains hitherto classified as type I are, in fact, quite heterogeneous, and several cluster with our newly defined genotypes V and VI. The sequence information needed for assigning genotypes can be captured by VP1, VP2, VP3, or large T-gene sequencing. The most polymorphic coding region in the viral genome is VP1, but significant variation is also present in the large T-antigen gene, wherein polymorphisms are found in 11.39% of all nucleotide sites, 46.22% of which are cluster specific. Type-specific amino acid changes within the VP1 region are predicted to map to the BC and DE loops. The number of taxonomically informative amino acid changes in the large T antigen exceeds even that of the VP1 region. Viral strains isolated from healthy subjects and from patients with human immunodeficiency virus infection, WiskottAldrich syndrome, and vasculopathy with capillary leak syndrome formed distinct subclusters. However, within the kidney transplant population, BKV strains derived from patients with asymptomatic viruria did not show complete separation from strains associated with allograft nephropathy.Polyomavirus BK (BKV) has a worldwide seroprevalence of 60 to 80% in humans (10). Primary infection occurs in childhood (11) and leads to viral latency in the urogenital tract and mononuclear cells. Following reactivation, which mostly occurs in immunocompromised patients, the virus is excreted in the urine (5). BKV viruria in renal transplant recipients ranges between 10 to 60% and has been associated with ureteric stenosis (16) and BK viral nephropathy characterized by tubular necrosis and interstitial nephritis (32, 33). In bone marrow transplant recipients, BKV has been linked to hemorrhagic cystitis (13,26,34).Characterization of genetic diversity of BK virus has biologic as well as clinical implications. This information is needed to seek potential relationships between viral genotype and clinical disease. Sequence data are required by diagnostic virology laboratories to ensure that primers and probes being used for amplification of viral DNA can successfully detect all naturally occurring viral strains. One of the most variable regions of the viral genome is the noncoding control region (NCCR), which shows insertions, deletions, duplications, and complex rearrangements involving enhancer and/or promoter sequences (28, 29). Significant variation is also recognized in the VP1 gene, which codes for VP1, a major structural protein that comprises approximately 80% of the total viral c...

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Phylogenetic Analysis of Polyomavirus BK Sequences

Sharma

Gupta

Vats

et al. 2006

J Virol

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“…2,14,[26][27][28] Although HC can be secondary to a variety of factors (drugs, radiation, infections), HC in the BMT setting is usually either related to the use of CY or, later in the course of the transplant, to viral infections. [2][3][4][5][6][7][8]14 CY has been widely used for conditioning patients for BMT. Methods commonly used for prophylaxis of HC in BMT patients are intravenous hyperhydration (IVH), continuous bladder irrigation (CBI) and, more recently Mesna.…”

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Risk factors for severe hemorrhagic cystitis following BMT

Seber

Shu

DeFor

et al. 1998

Bone Marrow Transplant

155

137

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Summary:Hemorrhagic cystitis (HC) is a common toxicity of preparative regimens for bone marrow transplantation (BMT). Severe HC often requires prolonged and expensive hospitalization, and occasionally can result in death. To investigate the risk factors for severe HC, we conducted a retrospective study among 1908 patients who received BMTs at the University of Minnesota during 1974 to 1993. A previous report from our institution reported on 977 of these patients. We identified all patients with genitourinary complication within 100 days post-BMT from the BMT database. Medical charts for these patients were reviewed to determine whether the patient had HC and also the grade of HC. A total of 208 HC cases were identified during the study period. Of them, 92 patients had severe HC, an incidence of 5% (95% CI = 4-6%). We found that grade II-IV graftversus-host disease (RR = 2.56; 95% CI = 1.43-4.56), use of busulfan (RR = 2.69; 95% CI = 1.35-5.35), and age at transplant (RR = 2.20; 95% CI = 1.27-3.81, for age of 10-30 compared to age of 0-9) were related to an increased risk of HC. In contrast, transplant year was inversely associated with the risk of HC (trend test, P Ͻ 0.01). We did not find any significant difference in HC with the use of prophylactic Mesna. Keywords: bone marrow transplantation; complications; hemorrhagic cystitis; risk factors; adenovirus; cytomegalovirus Outcome after bone marrow transplantation (BMT) has improved over the past 20 years, 1 but preparative regimenrelated toxicities (RRT) remain a major limitation to further progress. Hemorrhagic cystitis (HC) is a common RRT. 2 In the BMT setting, HC occurring in the early post-transplant period is more frequently associated with the use of cyclophosphamide (CY), while late occurring HC frequently results from viral infections (eg BK virus, adenovirus type II). 3-8 CY has been widely used for conditioning patients undergoing BMT. The drug is hydroxylated in the liver, generating 4 hydroxy-CY, phosphoramide mustard, and acrolein. Excreted in the urine, acrolein can cause edema,

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“…Postinfection, BKV establishes a persistent, but usually silent infection within epithelial tissue of the kidney (19,22). In the context of an impaired immune system, the lytic nature of this virus in combination with the host inflammatory response can cause multiple diseases such as hemorrhagic cystitis, retinitis, meningoencephalitis, and interstitial nephritis (4,5,24,25). Polyomavirus-associated nephropathy, is a complication in 5% of kidney transplantations induced by elevated BKV replication (23).…”

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Identification of Amino Acid Residues in BK Virus VP1 That Are Critical for Viability and Growth

Dugan¹,

Gasparovic

Tsomaia

et al. 2007

J Virol

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BK virus (BKV) is a ubiquitous pathogen that establishes a persistent infection in the urinary tract of 80%of the human population. Like other polyomaviruses, the major capsid protein of BKV, virion protein 1 (VP1), is critical for host cell receptor recognition and for proper virion assembly. BKV uses a carbohydrate complex containing ␣(2,3)-linked sialic acid attached to glycoprotein and glycolipid motifs as a cellular receptor. To determine the amino acids important for BKV binding to the sialic acid portion of the complex, we generated a series of 17 point mutations in VP1 and scored them for viral growth. The first set of mutants behaved identically to wild-type virus, suggesting that these amino acids were not critical for virus propagation. Another group of VP1 mutants rendered the virus nonviable. These mutations failed to protect viral DNA from DNase I digestion, indicating a role for these domains in capsid assembly and/or packaging of DNA. A third group of VP1 mutations packaged DNA similarly to the wild type but failed to propagate. The initial burst size of these mutations was similar to that of the wild type, indicating that there is no defect in the lytic release of the mutated virions. Binding experiments revealed that a subset of the BKV mutants were unable to attach to their host cells. These motifs are likely important for sialic acid recognition. We next mapped these mutations onto a model of BKV VP1 to provide atomic insight into the role of these sites in the binding of sialic acid to VP1.

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Bk Virus as Cause of Haemorrhagic Cystitis After Bone Marrow Transplantation

Cited by 38 publications

References 2 publications

Phylogenetic Analysis of Polyomavirus BK Sequences

Phylogenetic Analysis of Polyomavirus BK Sequences

Risk factors for severe hemorrhagic cystitis following BMT

Identification of Amino Acid Residues in BK Virus VP1 That Are Critical for Viability and Growth

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