BK and JC Virus Infections in Recipients of Bone Marrow Transplants

Arthur, Ray R.; Shah, Keerti V.; Charache, Patricia; Saral, Rein

doi:10.1093/infdis/158.3.563

Cited by 155 publications

(85 citation statements)

References 24 publications

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“…Some patients with severe HC had positive urine cultures for viruses as previously reported. 7,36,37 CMV was also more frequently found in the urine of patients with HC.…”

Section: Discussionmentioning

confidence: 92%

Risk factors for severe hemorrhagic cystitis following BMT

Seber

Shu

DeFor

et al. 1998

Bone Marrow Transplant

155

144

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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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“…Some patients with severe HC had positive urine cultures for viruses as previously reported. 7,36,37 CMV was also more frequently found in the urine of patients with HC.…”

Section: Discussionmentioning

confidence: 92%

Risk factors for severe hemorrhagic cystitis following BMT

Seber

Shu

DeFor

et al. 1998

Bone Marrow Transplant

155

144

View full text Add to dashboard Cite

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“…Although BKV infection remains asymptomatic throughout the lifetime of most humans, immunocompromised individuals are susceptible to BKV-induced disease. Reactivation of BKV has been linked to hemorrhagic cystitis in bone marrow transplant recipients and is the etiological agent of polyomavirus-induced nephropathy (PVN), 2 a complication found in 5% of kidney transplant recipients (4,5). In PVN, BKV induces interstitial nephritis resulting in graft destruction and leads to transplant failure in ϳ50% of diagnosed cases (6,7).…”

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confidence: 99%

Human α-Defensins Inhibit BK Virus Infection by Aggregating Virions and Blocking Binding to Host Cells

Dugan

Maginnis

Jordan

et al. 2008

Journal of Biological Chemistry

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BK virus (BKV) is a polyomavirus that establishes a lifelong persistence in most humans and is a major impediment to success of kidney grafts. The function of the innate immune system in BKV infection and pathology has not been investigated. Here we examine the role of antimicrobial defensins in BKV infection of Vero cells. Our data show that ␣-defensin human neutrophil protein 1 (HNP1) and human ␣-defensin 5 (HD5) inhibit BKV infection by targeting an early event in the viral lifecycle. HD5 treatment of BKV reduced viral attachment to cells, whereas cellular treatment with HD5 did not. Colocalization studies indicated that HD5 interacts directly with BKV. Ultrastructural analysis revealed HD5-induced aggregation of virions. HD5 also inhibited infection of cells by other related polyomaviruses. This is the first study to demonstrate polyomavirus sensitivity to defensins. We also show a novel mechanism whereby HD5 binds to BKV leading to aggregation of virion particles preventing normal virus binding to the cell surface and uptake into cells.BK virus is a member of the polyomaviridae family. Polyomaviruses are small (40 -50 nm in diameter), non-enveloped, double-stranded DNA viruses that cause tumors in some species outside of their natural host range (1). BKV infects ϳ80 -90% of the human population and establishes a lifelong persistence within epithelial cells of the urinary tract (2, 3). Although BKV infection remains asymptomatic throughout the lifetime of most humans, immunocompromised individuals are susceptible to BKV-induced disease. Reactivation of BKV has been linked to hemorrhagic cystitis in bone marrow transplant recipients and is the etiological agent of polyomavirus-induced nephropathy (PVN), 2 a complication found in 5% of kidney transplant recipients (4, 5). In PVN, BKV induces interstitial nephritis resulting in graft destruction and leads to transplant failure in ϳ50% of diagnosed cases (6, 7). BKV reactivation causes a serious viral infection after renal transplantation and is a significant obstacle to the success of kidney grafts.The factors that contribute to BKV-induced disease are largely unknown. As only a subset of kidney transplant recipients develop PVN, this raises the question of what unique factors are present in these situations for pathogenesis to ensue? The factors that contribute to PVN likely comprise multiple conditions that involve the virus, the host, and the graft. Some risk factors for the development of PVN include male gender, older age, and higher number of HLA mismatches (7, 8). Epidemiological studies suggest that the most significant cofactor leading to PVN is the degree of immunosuppression. The rise in PVN diagnoses is directly correlated to the increased use of the more potent anti-rejection drugs, tacromilus and mycophenolate mofetil (9, 10). Currently, a reduction of immunosuppressive therapy is effectively used to decrease viral replication in PVN patients suggesting that a functional immune system is critical in controlling BKV replication and pathology (11). ...

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“…1 Reactivation following BMT has been reported to be associated with haemorrhagic cystitis (HC). [2][3][4][5][6][7][8][9] HC is a serious post-transplant complication associated with significant morbidity. However, the relation between HC and polyoma virus remains contentious because not all patients who reactivate the virus develop HC.…”

mentioning

confidence: 99%