Possible antiviral effect of ciprofloxacin treatment on polyomavirus BK replication and analysis of non-coding control region sequences

Abstract

Acute renal dysfunction (ARD) is a common complication in renal transplant recipients. Multiple factors contribute to ARD development, including acute rejection and microbial infections. Many viral infections after kidney transplantation result from reactivation of "latent" viruses in the host or from the graft, such as the human Polyomavirus BK (BKV). We report the case of a 39 year-old recipient of a 2nd kidney graft who experienced BKV reactivation after a second episode of acute humoral rejection. A 10-day treatment with the quinolone antibiotic ciprofloxacin was administered with an increase of immunosuppressive therapy despite the active BKV replication. Real Time PCR analysis performed after treatment with ciprofloxacin, unexpectedly showed clearance of BK viremia and regression of BK viruria. During the follow-up, BK viremia persisted undetectable while viruria decreased further and disappeared after 3 months.BKV non-coding control region sequence analysis from all positive samples always showed the presence of archetypal sequences, with two single-nucleotide substitutions and one nucleotide deletion that, interestingly, were all representative of the subtype/subgroup I/b-1 we identified by the viral protein 1 sequencing analysis.We report the potential effect of the quinolone antibiotic ciprofloxacin in the decrease of the BKV load in both blood and urine.

Figure 1

Time course of clinical events and laboratory examinations.

Figure 2

Histopathological examination by Periodic Acid Schiff reaction, x200. Glomeruli are characterized by widespread, intense mononuclear infiltration, moderate increase of the matrix and focal pericapsular fibrosis. Arteries show intense intimal fibrosis and fragmentation of the internal elastic lamina, arterioles are characterized by intense intimal hyalinosis. Edema and inflammatory infiltration of lymphocytes without plasmacells are present in the interstitium. Peritubular capillaries are markedly dilated with leucocytes margination. Epithelium of the proximal tubules occurs frequently flattened; into the lumen of the distal tubules, sometimes dilated, are contained hyaline casts. No nuclear inclusions are detected in the tubular epithelium. Search for C4d, evaluated by immunohistochemistry on tissue sections fixed, was positive (+ +) on the walls of peritubular capillaries.

Figure 3

Alignment of BKV prototypic NCCR sequence with archetypal WW NCCR sequences detected in our patient. The prototypic (proto) NCCR is shown at the top of the figure and the BKV archetype WW strain NCCR consensus sequence (GenBank accession no. AB211371), belonged to subtype I subgroup b-1, we found in urine and blood specimens is shown below in relation to the prototypic NCCR, with similar nucleotides indicated by hyphens and the deletion identified by a triangle. Blocks (O, P, Q, R and S) commonly used to denote archetypal NCCRs [35] are indicated below the prototypic NCCR sequence.