Suppression of BK virus replication and cytopathic effect by inhibitors of prokaryotic DNA gyrase

Portolani, M.; Pietrosemoli, Paola; Cermelli, Claudio; Mannini-Palenzona, A; Grossi, Maria Pia; Paolini, Lorella; Barbanti‐Brodano, Giuseppe

doi:10.1016/0166-3542(88)90004-6

Cited by 76 publications

(60 citation statements)

References 28 publications

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“…Cidofovir should be used with caution, frequent monitoring, and informed consent because of the potential complications (109,110). Quinolones, DNA gyrase inhibitors, may interfere with the large T antigen helicase activity (111) and have in vitro and in vivo activity against BKV (112)(113)(114). Two months after a 10-d course of gatifloxacin, seven of 10 recipients with active BKV replication had reduction in viremia or urinary decoy cells (115).…”

Section: Adjuvant Therapiesmentioning

confidence: 99%

BK Virus Nephropathy and Kidney Transplantation

Bohl

Brennan

2007

Clinical Journal of the American Society of Nephrology

222

175

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Nephropathy from BK virus (BKV) infection is an evolving challenge in kidney transplant recipients. It is the consequence of modern potent immunosuppression aimed at reducing acute rejection and improving allograft survival. Untreated BKV infections lead to kidney allograft dysfunction or loss. Decreased immunosuppression is the principle treatment but predisposes to acute and chronic rejection. Screening protocols for early detection and prevention of symptomatic BKV nephropathy have improved outcomes. Although no approved antiviral drug is available, leflunomide, cidofovir, quinolones, and intravenous Ig have been used. Retransplantation after BKV nephropathy has been successful.Clin J Am Soc Nephrol 2: S36 -S46, 2007. doi: 10.2215/CJN.00920207 P olyomavirus infection in kidney transplant recipients is of increasing interest and research. Although the two human polyomaviruses, BK virus (BKV) and JC virus (JCV), were reported in 1971 (1,2), their influence and importance were limited. The emergence of polyomavirus nephropathy has coincided with the use of new potent immunosuppressive medications (3,4). It is usually associated with BKV, affects up to 8% of recipients, and frequently results in allograft loss or permanent dysfunction (5). It presents as an asymptomatic gradual rise in creatinine with a tubulointerstitial nephritis that mimics rejection, producing a treatment dilemma. The decrease in immunosuppression that is needed to treat infection is opposite to the increases that are needed to treat rejection.Two studies in kidney transplant recipients who were treated with prednisone and azathioprine in the early 1980s have provided the foundation for much of our current understanding of polyomaviruses in transplant recipients. Hogan et al. (6) and Gardner et al. (7) found that the pretransplantation seroprevalence was 80 to 88% for BKV and 54 to 55% for JCV. The posttransplantation rates of polyomavirus infection were 18 to 44% for BKV and 30 to 35% for JCV. Most polyomavirus infections were asymptomatic and occurred within the first 3 mo after transplantation. BKV infection was associated with a rising creatinine. More than 20 yr ago, Gardner et al. (7) warned, "The detection of polyomavirus infection is important as increased immunosuppression needs to be avoided to prevent possible complications."

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Section: Adjuvant Therapiesmentioning

confidence: 99%

BK Virus Nephropathy and Kidney Transplantation

Bohl

Brennan

2007

Clinical Journal of the American Society of Nephrology

222

175

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“…Fluoroquinolones display anti-BK properties through inhibition of DNA topoisomerase and polyomavirus associated large T-antigen helicase (2,16). An in vitro analysis using older fluoroquinolone compounds, nalidixic acid and oxolinic acid, demonstrated that these agents are capable of inhibiting BKV DNA replication (20). In another analysis using contemporary fluoroquinolones (i.e., levofloxacin, trovafloxacin, ciprofloxacin, ofloxacin, and gatifloxacin), it was shown that these antibiotics have the ability to inhibit viral DNA replication and T-antigen helicase activity of SV40 (21).…”

mentioning

confidence: 99%

Evaluation of Fluoroquinolones for the Prevention of BK Viremia after Renal Transplantation

Gabardi

Waikar²,

Martin³

et al. 2010

Clinical Journal of the American Society of Nephrology

101

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Background and objectives: Nearly 30% of renal transplant recipients develops BK viremia, a prerequisite for BK nephropathy. Case reports have evaluated treatment options for BK virus, but no controlled studies have assessed prophylactic therapies. Fluoroquinolone antibiotics were studied for prevention of BK viremia after renal transplantation.Design, setting, participants, & measurements: This retrospective analysis evaluated adult renal transplant recipients with at least one BK viral load (blood) between 90 and 400 days after transplantation. Six to 12 months of co-trimoxazole was used for Pneumocystis prophylaxis. In sulfa-allergic/-intolerant patients, 6 to 12 months of atovaquone with 1 month of a fluoroquinolone was used. Fluoroquinolones can inhibit BK DNA topoisomerase. The two groups studied were those that received 30 days of levofloxacin or ciprofloxacin after transplantation and those that did not. The primary endpoint was BK viremia rates at 1 year. Of note, of the 160 patients not receiving fluoroquinolone prophylaxis, 40 received a fluoroquinolone for treatment of a bacterial infection within 3 months after transplantation. Subgroup analysis evaluating these 40 patients against the 120 who had no exposure to fluoroquinolones was completed.Results: A 1-month fluoroquinolone course after transplantation was associated with significantly lower rates of BK viremia at 1 year compared with those with no fluoroquinolone. In the subgroup analysis, exposure to fluoroquinolone for treatment of bacterial infections within 3 months after transplantation was associated with significantly lower 1-year rates of BK viremia.Conclusions: This analysis demonstrates that fluoroquinolones are effective at preventing BK viremia after renal transplantation.

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“…Nalidixic acid behaved quite differently, for it inhibited SV40 replication at concentrations that only slightly affect cell growth and synthesis of cellular DNA. In any case, the selectivity exhibited is much lower than the one found by Portolani et al (1988). Although Nalidixic acid has been previously reported to influence the activity of topoisomerase II in mammalian cells (Mattern et al, 1981), it does so at concentrations exceeding 1 mM (>200mg 1-…”

Section: Dna Protein Cross-links (Ope)mentioning

confidence: 58%

“…Nalidixic acid and Oxolinic acid, both inhibitors of bacterial DNA gyrase (a topoisomerase II enzyme), have been reported to effectively reduce the growth of BK virus, a member of Papovaviridae closely related to SV40, without relevant signs of cytotoxicity (Portolani et al, 1988). The possibility of an interference with topoisomerase II was hence raised as a mechanism of selective viral growth inhibition.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Topoisomerase Inhibitors as Potential Antiviral Agents

Maschera

Ferrazzí

Rassu

et al. 1993

Antivir Chem Chemother

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SummaryAnti-eukaryotic topoisomerase drugs, Camptothecin and Etoposide, were tested for their ability of selectively interfering with the replication of simian virus 40 (SV40) DNA. Nalidixic acid was also assayed for a comparison, since the compound has been previously reported to affect papoyijvirus growth. Our results indicate that anti-eukary6tic topoisomerase drugs significantly inhibit viral DNA replication but at . concentrations that are also toxic for uninfected cells. Etoposide treatment produced a relatively higher number of DNA-protein cross-links in virus-infected cells as compared to un infected control cells. Nalidixic acid displayed some degree of selectivity for inhibiting SV40 DNA synthesis more effectively than synthesis of cellular DNA without appreciable reduction of cell growth. This activity does not appear to depend on DNA damage or interference with topoisomerase II and deserves further evaluation.

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Suppression of BK virus replication and cytopathic effect by inhibitors of prokaryotic DNA gyrase

Cited by 76 publications

References 28 publications

BK Virus Nephropathy and Kidney Transplantation

BK Virus Nephropathy and Kidney Transplantation

Evaluation of Fluoroquinolones for the Prevention of BK Viremia after Renal Transplantation

Evaluation of Topoisomerase Inhibitors as Potential Antiviral Agents

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