The persistence of papovavirus BK DNA sequences in normal human renal tissue

Chesters, P. M.; McCance, Dennis J.

doi:10.1002/jmv.1890080208

Cited by 195 publications

(105 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[13][14][15] Primary infection occurs in childhood and remains in a latent phase most commonly in the kidney. [16][17][18][19] The reactivation of the latent virus is observed in patients with immunodeficiency. 19,20 The two most important diseases are BKV-associated nephropathy in renal transplant and BKV-associated HC (BK-HC) in allo-HSCT.…”

Section: Introductionmentioning

confidence: 99%

The risk of polyomavirus BK-associated hemorrhagic cystitis after allogeneic hematopoietic SCT is associated with myeloablative conditioning, CMV viremia and severe acute GVHD

Uhm

Hamad

Michelis

et al. 2014

Bone Marrow Transplant

View full text Add to dashboard Cite

Hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic SCT (allo-HSCT). Several risk factors have been suggested including BU-containing myeloablative conditioning, unrelated donors and GVHD, but these have not been consistently reported. We conducted a retrospective study including 339 allo-HSCT recipients between 2009 and 2012. Of 339 patients, 79 (23.3%) developed HC with 2-year cumulative incidence of 24.0% (95% confidence interval, 19.4-28.9). The median onset time was 45 days (range, 16-430) after allo-HSCT. Sixty-two patients (84%) out of 74 evaluated for urine BK virus PCR testing showed a positive result (mean 2.0 × 10 10 copies of DNA per mL). In univariate analysis, myeloablative conditioning, HLA-mismatched donor, CMV viremia and acute GVHD (aGVHD) grade 3-4 were significantly associated with the risk of HC. Multivariate analysis confirmed all associating factors identified in univariate analysis except for HLA-mismatched donor: myeloablative conditioning (hazard ratio (HR) 2.63, P = 0.003), CMV viremia (HR 1.88, P = 0.014) and aGVHD grade 3-4 (HR 1.71, P = 0.029). HC did not affect OS or non-relapse mortality. Symptomatic HC is a frequent complication following allo-HSCT, with a 2-year cumulative incidence of 24.0%. Three clinical factors associated with HC were identified including myeloablative conditioning, CMV viremia and severe aGVHD.

show abstract

Section: Introductionmentioning

confidence: 99%

The risk of polyomavirus BK-associated hemorrhagic cystitis after allogeneic hematopoietic SCT is associated with myeloablative conditioning, CMV viremia and severe acute GVHD

Uhm

Hamad

Michelis

et al. 2014

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…Primary infection with JCV usually occurs during childhood and is asymptomatic (Padgett & Walker 1973). At the site of entry, which is normally the respiratory tract, these viruses replicate and traffic to the tissues of the kidneys (Heritage et al 1981, McCance 1983) and the central nervous system, where they sustain a long-term infection (Elsner & Dörries 1992, Quinlivan et al 1992. A recurrence of the infection may be induced by significant immunosuppression, as in the case of kidney (Hogan et al 1980, Kahan et al 1980, Gardner et al 1984) and bone marrow transplants (O'Reilly et al 1981, Arthur et al 1988) and other factors such as immunodeficiency diseases, diabetes, other chronic diseases, immunosuppressive chemotherapy, pregnancy ) and old age (Tajima et al 1990).…”

mentioning

confidence: 99%

JC polyomavirus infection in candidates for kidney transplantation living in the Brazilian Amazon Region

Melo¹,

Bezerra

Ishak

et al. 2013

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

“…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.…”

mentioning

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

View full text Add to dashboard Cite

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). ...

show abstract

The persistence of papovavirus BK DNA sequences in normal human renal tissue

Cited by 195 publications

References 19 publications

The risk of polyomavirus BK-associated hemorrhagic cystitis after allogeneic hematopoietic SCT is associated with myeloablative conditioning, CMV viremia and severe acute GVHD

The risk of polyomavirus BK-associated hemorrhagic cystitis after allogeneic hematopoietic SCT is associated with myeloablative conditioning, CMV viremia and severe acute GVHD

JC polyomavirus infection in candidates for kidney transplantation living in the Brazilian Amazon Region

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

Contact Info

Product

Resources

About