RESEARCH PAPER
Antiviral activity of ciprofloxacin on BK virus in an in vitro culture – pilot study
 
More details
Hide details
1
Department of Virology, Medical University of Lublin
CORRESPONDING AUTHOR
Justyna Pasternak   

Department of Virology, Medical University of Lublin, Witolda Chodźki 1, 20-093 Lublin, Poland
 
J Pre Clin Clin Res. 2017;11(2):116–119
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Reactivation of BKV infection caused by decrease of immunity associated with organ transplantation can lead to nephropathy and organ loss. Antiviral drugs such as ganciclovir or foscarnet did not display any activity against BK virus. A source of hope can be found in chemotherapeutics usually used in bacterial infections that inhibit the replication of viral genetic material in cells. One of the aforementioned chemotherapeutics is ciprofloxacin. The aim of the study is to evaluate the antiviral activity of ciprofloxacin against BK virus in vitro culture.

Material and methods:
Initially, the effects of ciprofloxacin on Vero cell viability were assessed with MTT. After determining the 3 largest non-cytotoxic concentrations of antibiotics, their effect on viral replication in cells was determined. 24-h cells culture in DMEM medium supplemented with 10% serum after 2h incubation with a 6.3 x 105 copies/ml infection virus were used to evaluate the effects of different concentrations of ciprofloxacin on the number of BKV copies. Quantification of BKV replication in the culture was performed by real-time PCR.

Results:
By means of the MTT test, the 3 largest non-cytotoxic ciprofloxacin concentrations were determined as follows: 31.25; 62.5; 125 μg/ml. Cells treated with ciprofloxacin at a concentration of 125 μg/ml display the greatest decrease in BKV replication that equaly 1.8 – 3 log/5.8 – 9.2 Ct, compared to the control of the virus without drugs. A decline in the number of copies of the virus was observed during the lower concentration of the antibiotic (62.5, 31.25 μg/ml) by 1.3 – 2 log/4 – 6.4 Ct and 0 – 0.8 log/0 – 2, 4 Ct, respectively.

Conclusions:
Ciprofloxacin exhibits antiviral activity against the BK virus by inhibiting its replication in the in vitro culture in Vero cell line.

 
REFERENCES (20)
1.
Świątek Ł, Polz-Dacewicz M. Polyomaviruses as etiological agents of human diseases – a review. In Polz-Dacewicz M, editor. Viral infection – diagnostics, prevention and control: the role of viral infection in public health. Lublin; 2010; p. 29–36.
 
2.
Jozpanahi M, Ramezani A, Ossareh S, Banifazl M, Bavand A, Mamishi S et al. BK Viremia among Iranian Renal Transplant Candidates. Iran J Pathol. 2016; 11(3): 210–215.
 
3.
Jeffers-Francis LK, Burger-Calderon R, Webster-Cyriaque J. Effect of Leflunomide, Cidofovir and Ciprofloxacin on replication of BKPyV in a salivary gland in vitro culture system. Antiviral Res. 2015; 118: 46–55.
 
4.
Flores V, Rodríguez-Sánchez B, Marín-Jiménez I, Bouza E, Menchén L, Muñoz P. Prospective Study of BK Virus Infection in Patients with Inflammatory Bowel Disease. The Scientific World Journal, vol. 2014, Article ID 970528, 6 pages, 2014. doi:10.1155/2014/970528.
 
5.
Hariharan S. BK virus nephritis after renal transplantation. Kidney Int. 2006; 69(4): 655–662.
 
6.
Acott PD, O’Regan PA, Lee SH, Crocker JF. Utilization of Vero cells for primary and chronic BK virus infection. Transplant Proc. 2006; 38(10): 3502–3505.
 
7.
Ali SH, Chandraker A, DeCaprio JA. Inhibition of Simian virus 40 large T antigen helicase activity by fluoroquinolones. Antivir Ther. 2007; 12: 1–6.
 
8.
Arthur RR, Dagostin S, Shah KV. Detection of BK virus and JC virus in urine and brain tissue by the polymerase chain reaction. Journal of Clinical Microbiology. 1989; 27(6): 1174–1179.
 
9.
Matłosz B, Durlik M. Śródmiąższowe zapalenie nerki przeszczepionej wywołane wirusem Polyoma BK. Przegl Eidemiol. 2006; 60(1): 133–140.
 
10.
Longhi G, Pietropaolo V, Mischitelli M, Longhi C, Conte MP, Marchetti M, Tinari A, Valenti P, Degener AM, Seganti L, Superti F. Lactoferrin inhibits early steps of human BK polyomavirus infection. Antiviral Res. 2006; 72:145–152.
 
11.
Rinaldo CH, Gosert R, Bernhoff E, Finstad S, Hirsch HH. 1-O-hexadecyloxypropyl cidofovir (CMX001) effectively inhibits polyomavirus BK replication in primary human renal tubular epithelial cells. Antimicrob Agents Chemother. 2010; 54: 4714–4722.
 
12.
Farasati NA, Shapiro R, Vats A, Randhawa P. Effect of leflunomide and cidofovir on replication of BK virus in an in vitro culture system. Transplantation. 2005; 79: 116–118.
 
13.
Bernhoff E, Tylden GD, Kjerpeseth LJ, Gutteberg TJ, Hirsch HH, Rinaldo C.H. Leflunomide inhibition of BK virus replication in renal tubular epithelial cells. J Virol. 2010; 84: 2150–2156.
 
14.
Bernhoff E, Gutteberg TJ, Sandvik K, Hirsch HH, Rinaldo CH. Cidofovir inhibits polyomavirus BK replication in human renal tubular cells downstream of viral early gene expression. Am J Transplant. 2008; 8: 1413–1422.
 
15.
Leung AY, Chan MT, Yuen KY, Cheng VC, Chan KH, Wong CL et al. Ciprofloxacin decreased polyoma BK virus load in patients who underwent allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. 2005; 40: 528–537.
 
16.
Gabardi S, Waikar SS, Martin S, Roberts K, Chen J, Borgi L et al. Evaluation of fluoroquinolones for the prevention of BK viremia after renal transplantation. Clin J Am Soc Nephrol. 2010; 5(7): 1298–1304.
 
17.
Sharma PM, Gupta G, Vats A, Shapiro R, Randhawa PS. Polyomavirus BK non-coding control region rearrangements in health and disease. J Med Virol. 2007; 79: 1199–1207.
 
18.
Jin L, Gibson PE, Knowles WA, Clewley JP. BK virus antigenic variants: sequence analysis within the capsid VP1 epitope. J Med Virol. 1993; 39: 50–56.
 
19.
Karalic D, Lazarevic I, Banko A, Cupic M, Jevtovic D, Jovanovic T. Molecular characterization of BK virus in patients infected with human immunodeficiency virus. Med Microbiol Immunol. 2016; 205(2):185–193.
 
20.
Wojciechowski D, Chanda R, Chandran S, Lee B, Webber A, Macaraig M et al. Ciprofloxacin prophylaxis in kidney transplant recipients reduces BK virus infection at 3 months but not at 1 year. Transplantation. 2012; 94(11): 1117–1123.
 
eISSN:1898-7516
ISSN:1898-2395