Polymorphisms of the BK virus subtypes and their influence on viral in vitro growth efficiency

Tremolada, Sara; Delbue, Serena; Larocca, Sara; Carloni, Camilla; Elia, Francesca; Khalili, Kamel; Gordon, Jennifer; Ferrante, Pasquale

doi:10.1016/j.virusres.2010.01.017

Cited by 26 publications

(22 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Polyomavirus of the family Polyomaviridae which also includes JCV, SV40 and the newly discovered WI, KU, and MC viruses [Tremolada et al, 2010]. BKV infection is generally acquired in childhood and is usually asymptomatic.…”

Section: Bk Polyomavirus (Bkv) Is a Member Of The Genusmentioning

confidence: 99%

Molecular characterization of BK polyomavirus subtypes in renal transplant recipients in Brazil

Zalona

Santoro‐Lopes

Schrago

et al. 2011

Journal of Medical Virology

View full text Add to dashboard Cite

BK polyomavirus (BKV) is highly prevalent in the world population. Different reports indicate that BKV subtypes and subgroups present an uneven geographical distribution which might be correlated with human migration. However, there is a lack of data on the BKV subtype distribution in the South American population. The occurrence of BKV subtypes and subgroups detected in 51 kidney transplant recipients in Rio de Janeiro, Brazil is described. According to genetic studies, the population in this region descends mainly from European or African immigrants, with a relatively low genetic background from the Amerindians. By sequencing the VP1 region of BKV, subgroups Ib1 and Ia of subtype I were found in 34 (67%) and 15 (29%), respectively, of samples, while subtype II was present in 2 (4%) of the samples. Subtypes III and IV were not detected. Phylogenetic analysis indicated similarities between Brazilian BKV subgroup Ia and East African lineages; and subgroup Ib-1 with Asian and North American lineages, while subtype II samples were similar to sequences from Japan and the UK. This is the first report that describes distribution of BKV subtypes in South America. The high prevalence of BKV subgroup Ia probably reflects the high proportion of African descendants in this population. On the other hand, the predominance of subgroup Ib-1 and the absence of Ib-2 in an area with a high proportion of European ancestry was unexpected. Further studies in South American populations are needed to provide a better understanding of the epidemiology of BKV in this region.

show abstract

Section: Bk Polyomavirus (Bkv) Is a Member Of The Genusmentioning

confidence: 99%

Molecular characterization of BK polyomavirus subtypes in renal transplant recipients in Brazil

Zalona

Santoro‐Lopes

Schrago

et al. 2011

Journal of Medical Virology

View full text Add to dashboard Cite

show abstract

“…Indeed, cell culture studies have underscored the importance of the VP1 composition for propagation of BKV. In human renal epithelial cells, subtype I strains grew more efficiently than subtype IV strains (Nukuzuma et al, 2006), while in Vero cells, subtype III displayed lower replication capacity than the other subtypes (Tremolada et al, 2010c). A study of Vero cells infected with BKV mutants containing substitutions in several charged amino acids within VP1 loops BC, DE, and HI showed that some of these mutants were deficient in genome packaging, capsid assembly, or binding to host cells (Dugan et al, 2007).…”

mentioning

confidence: 99%

BK virus‐associated infection in cerebrospinal fluid of neurological patients and mutation analysis of the complete VP1 gene in different patient groups

Bárcena-Panero

Ghelue

Khan

et al. 2011

Journal Cellular Physiology

View full text Add to dashboard Cite

While BK virus (BKV) is frequently associated with pathological conditions in bone marrow and renal transplant recipients, BKV infection in neurological individuals has been rarely reported. As a result of a BKV, JCV, and SV40 large T antigen-specific multiplex PCR on 2,062 cerebrospinal fluid (CSF) samples from neurological patients suspicious of JCV infection, we identified 20 subjects with at least 1 CSF specimen positive for BKV large T antigen DNA. Because VP1 protein has been suggested to influence the biological/pathological properties of BKV, we tried to sequence the entire VP1 gene in the BKV-positive neurological patients and succeeded in 14 of the 20 neurological patients. To compare the VP1 sequence of the BKV neurological strains with that of non-neurotropic strains in other clinical situations, full-length VP1 DNA was sequenced in 15 renal and 6 bone marrow transplant recipients positive to BKV-viremia, and in 8 pregnant women as non-pathological controls. An increased (respectively, decreased) tendency for mutations in the BC loop (respectively, EF loop) was observed, and no mutations were detected in the CD, GH, and HI loops. Subtype I was predominant (93%) and compared to archetypal BKV (WW), amino acid substitutions were detected in 4/14 neurological patients, 10/15 renal transplant recipients, 3/6 bone marrow transplant patients, and in all the pregnant women. Each patient group had distinctive VP1 mutations, but these unique substitutions were not present in all patients of this group. However, molecular modeling simulations of the VP1 mutants predicted changes in protein surface properties which might affect the VP1-receptor interaction.

show abstract

“…Subtypes II and III are rarely identified, though primer and/or probe subtype-specific mismatches in certain BKV molecular diagnostic assays may contribute to underdetection (1,10). Interestingly, BKV subtype III demonstrates reduced replicative capacity in vitro (11). This may correspond to limited pathogenicity in vivo and contribute to the low prevalence of BKV subtype III worldwide.…”

mentioning

confidence: 99%

“…We identified viral amino acid changes that are unique among BKV sequences, most of which affected the BC loop of VP1. It has been proposed that amino acid changes within the BC loop may be associated with an increase in pathogenic potential and therefore may contribute to the development of BKVN (11,12). In addition, phosphorylation has been hypothesized to influence VP1 function, and two of the amino acid changes (P59S and N61T) create potential new phosphorylation sites for cellular kinases (13).…”

mentioning

confidence: 99%

BK Polyomavirus Subtype III in a Pediatric Renal Transplant Patient with Nephropathy

et al. 2013

View full text Add to dashboard Cite

f BK polyomavirus (BKV) is an emerging pathogen in immunocompromised individuals. BKV subtype III is rarely identified and has not previously been associated with disease. Here we provide the whole-genome sequence of a subtype III BKV from a pediatric kidney transplant patient with polyomavirus-associated nephropathy. CASE REPORTA 16-year-old with a history of posterior urethral valves complicated by obstructive uropathy leading to end-stage renal disease received a kidney transplant from his father (living related donor) in 2000. He was maintained on steroid-free immunosuppression with tacrolimus and mycophenolate mofetil for 8 years. In 2008, the patient was diagnosed with chronic transplant glomerulopathy, eventually requiring dialysis. He received his second renal transplant in 2012 from a 1/6 human leukocyte antigen (HLA)-matched deceased male donor. He had a wide range of anti-HLA class I and II preformed antibodies with percent panel reactive antibody (%PRA) values of 13% class I and 69% class II. For induction immunosuppression, the patient received a total of 7.5 mg/kg (body weight) of rabbit antithymocyte globulin with methylprednisone premedication and a single dose of 500 mg/m 2 (body surface area) rituximab. He was maintained on immunosuppression consisting of tacrolimus, mycophenolate mofetil, and a tapering dose of prednisone. A ureteric stent placed routinely at the time of transplant was removed uneventfully at ϳ5 weeks posttransplant. BK polyomavirus (BKV) DNA was monitored regularly in plasma and urine specimens by quantitative real-time PCR. Testing was performed using the previously described V3a assay (1), modified for use on a LightCycler 2.0 instrument (see the supplemental material). BKV DNA was first noted in plasma on posttransplant day (PTD) 114. A renal biopsy was performed because of increasing creatinine and plasma BKV levels (293,000 BKV copies/ml on PTD 154, 5 days before the biopsy) despite decreased immunosuppression. The biopsy specimen showed histological evidence of severe tubulointerstitial inflammation, and immunohistochemistry using antibodies against simian virus 40 (SV40) T antigen (dilution, 1:200; EDTA antigen retrieval) (Calbiochem, USA) revealed frequent nuclear staining of tubular epithelial cells, confirming the presence of BKV antigen (Fig. 1). Taken together, these findings were diagnostic for severe BK virus-associated nephropathy (BKVN). BKV levels reached 1.2 million copies/ml in plasma (PTD 210) and Ͼ60 million copies/ml in urine (PTD 154). Levels remained at more than 10 4 copies/ml in serial plasma samples (n ϭ 17) collected up to PTD 308 (results

show abstract

Polymorphisms of the BK virus subtypes and their influence on viral in vitro growth efficiency

Cited by 26 publications

References 25 publications

Molecular characterization of BK polyomavirus subtypes in renal transplant recipients in Brazil

Molecular characterization of BK polyomavirus subtypes in renal transplant recipients in Brazil

BK virus‐associated infection in cerebrospinal fluid of neurological patients and mutation analysis of the complete VP1 gene in different patient groups

BK Polyomavirus Subtype III in a Pediatric Renal Transplant Patient with Nephropathy

Contact Info

Product

Resources

About