Recurring theme of changes in the transcriptional control region of BK virus during adaptation to cell culture

Rubinstein, Riva; Schoonakker, B C; Harley, Eric H.

doi:10.1128/jvi.65.3.1600-1604.1991

Cited by 50 publications

(16 citation statements)

References 23 publications

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“…The rapid emergence of rr-NCCR BKV variants with higher replicative capacity in immunosuppressed KT patients is reminiscent of rr-NCCR generation in tissue culture ( 26,27,42 ), and is in striking contrast to the stable colonization of the world ' s population with archetype ww-NCCR BKV strains that do not replicate as well ( 43,44 ). Indeed, our ongoing analysis of BKV seropositive healthy blood donors detected asymptomatic BKV viruria in 9.8%, with ww-NCCR in all cases.…”

Section: Discussionmentioning

confidence: 96%

Polyomavirus BK with rearranged noncoding control region emerge in vivo in renal transplant patients and increase viral replication and cytopathology

Gosert

Rinaldo

Funk

et al. 2008

The Journal of Experimental Medicine

194

231

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Immunosuppression is required for BK viremia and polyomavirus BK–associated nephropathy (PVAN) in kidney transplants (KTs), but the role of viral determinants is unclear. We examined BKV noncoding control regions (NCCR), which coordinate viral gene expression and replication. In 286 day–matched plasma and urine samples from 129 KT patients with BKV viremia, including 70 with PVAN, the majority of viruses contained archetypal (ww-) NCCRs. However, rearranged (rr-) NCCRs were more frequent in plasma than in urine samples (22 vs. 4%; P < 0.001), and were associated with 20-fold higher plasma BKV loads (2.0 × 104/ml vs. 4.4 × 105/ml; P < 0.001). Emergence of rr-NCCR in plasma correlated with duration and peak BKV load (R2 = 0.64; P < 0.001). This was confirmed in a prospective cohort of 733 plasma samples from 227 patients. For 39 PVAN patients with available biopsies, rr-NCCRs were associated with more extensive viral replication and inflammation. Cloning of 10 rr-NCCRs revealed diverse duplications or deletions in different NCCR subregions, but all were sufficient to increase early gene expression, replication capacity, and cytopathology of recombinant BKV in vitro. Thus, rr-NCCR BKV emergence in plasma is linked to increased replication capacity and disease in KTs.

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Section: Discussionmentioning

confidence: 96%

Polyomavirus BK with rearranged noncoding control region emerge in vivo in renal transplant patients and increase viral replication and cytopathology

Gosert

Rinaldo

Funk

et al. 2008

The Journal of Experimental Medicine

194

231

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“…The analysis of a fragment of the VP1 coding sequence helps to define the virus genotypes and their different distribution in the human populations [Stoner et al, 2000; Agostini et al, 2001a, b; Pagani et al, 2003; Yogo et al, 2009]. The origin of replication and the promoter region including binding sites for cell transcription factors are located in a region of approximately 400 bp, linked to a non‐coding control region, which may undergo rearrangements easily [Rubinstein et al, 1991; Elsner and Dorries, 1992; Johnsen et al, 1995; Ciappi et al, 1999; Vaz et al, 2000; Rinaldo et al, 2005].…”

Section: Discussionmentioning

confidence: 99%

Investigation of polyomaviruses replication in pediatric patients with nephropathy receiving rituximab

Delbue

Ferraresso

Elia

et al. 2012

Journal of Medical Virology

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Rituximab is a chimeric monoclonal antibody reacting with the CD20 antigen on B cells. It has been proposed as treatment for the idiopathic nephrotic syndrome, recurrent idiopathic nephropathy, and focal segmental glomerulosclerosis refractory to steroids. Rituximab influences T‐cell immunity and may predispose the patients to opportunistic infections, such as progressive multifocal leukoencephalopathy caused by the polyomavirus JC (JCV). The risk of latent viruses infections/reactivations in pediatric patients receiving monoclonal antibodies is not well known yet. In this longitudinal 6‐month study, the effects of rituximab on JCV and BK virus (BKV) replication have been investigated. Blood, serum, and urine samples have been collected monthly from 11 pediatric patients (mean age: 11 years) with the idiopathic nephrotic syndrome and recurrent idiopathic nephropathy, under rituximab therapy. JCV and BKV real‐time PCRs and sequencing of the viral protein 1 and the non‐coding control region have been conducted. The same investigations have been undertaken on samples collected from eight pediatric patients (controls, mean age: 6 years), with idiopathic nephrotic syndrome or focal segmental glomerulosclerosis, treated with conventional chemotherapy. JCV was detected in the urine of one patient (9%), and one control (12.5%); BKV was found in the urine of 7/11 patients (63.6%) and 2/8 controls (25%) and in blood samples from four patients. No significant difference was found in the mean viral loads and in the viral molecular characterizations between the two groups. The polyomaviruses replication was not associated with rituximab therapy in children. J. Med. Virol. 84:1464–1470, 2012. © 2012 Wiley Periodicals, Inc.

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“…It is commonly reported that the predominant NCCR configuration actively shed in urine is archetypal (Markowitz et al, 1991;Negrini et al, 1991;Sharma et al, 2007;Sundsfjord et al, 1999;Takasaka et al, 2004), and that NCCR rearrangements seem to be isolated more frequently from the tissues and sera of patients with high viral loads (Boldorini et al, 2001;Gosert et al, 2008;Stoner et al, 2002). In addition, changes in the NCCR structure arise spontaneously in tissue culture and these rearrangements enhance the ability of the virus to replicate and transform cells (Rubinstein et al, 1991;Watanabe and Yoshiike, 1985;Watanabe and Yoshiike, 1986). It is possible that changes in the viral promoter region can also result in altered pathogenesis, such as a heightened ability to reactivate or disseminate.…”

Section: Introductionmentioning

confidence: 99%

Transforming growth factor-beta-mediated regulation of BK virus gene expression

Abend¹,

Imperiale²

2008

Virology

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The increasing prevalence of BK virus (BKV)-associated diseases in immunosuppressed patients has prompted an investigation of the immune response to BKV, especially the role of cytokines in regulating viral replication. We examined the effect of TGF-beta, a cytokine that is stimulated by certain immunosuppressive therapies, on BKV gene expression during lytic infection of renal proximal tubule epithelial cells. Viral gene expression, and specifically the activity of the BKV early promoter, is regulated by TGF-beta in a strain-dependent manner. Promoter activity is upregulated in the presence of TGF-beta for the TU strain of BKV, and not for the Dik, Dunlop, or Proto-2 strains. Using site-directed mutagenesis, we have identified a small segment of the TU promoter that is required for stimulation in response to TGF-beta. These results demonstrate that BKV strains can respond differently to cytokine treatment and suggest that TGF-beta may play a role in the reactivation of BKV.

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Recurring theme of changes in the transcriptional control region of BK virus during adaptation to cell culture

Cited by 50 publications

References 23 publications

Polyomavirus BK with rearranged noncoding control region emerge in vivo in renal transplant patients and increase viral replication and cytopathology

Polyomavirus BK with rearranged noncoding control region emerge in vivo in renal transplant patients and increase viral replication and cytopathology

Investigation of polyomaviruses replication in pediatric patients with nephropathy receiving rituximab

Transforming growth factor-beta-mediated regulation of BK virus gene expression

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