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Keywords:

  • BK virus;
  • BKV;
  • mycophenolate mofetil;
  • mycophenolic acid;
  • polyomavirus

Summary

Consensus is lacking about which immunosuppressant agents potentiate BK virus infection. The effects of mycophenolic acid (MPA) were investigated in BK virus (BKV)-infected Vero E6 cells. MPA (1–16 mg/l) exhibited a dose-dependent anti-viral effect (101–104 fold reduction in BKV DNA copies/ml) in supernatant, similar to cidofovir (2.5–25 mg/l). This effect was observed for early and persistent infection, and infection with noncoding control region (NCCR) rearranged BKV. MPA reduced BKV DNA copies/ml by >1 log after day 14 in three patient isolates before and after NCCR rearrangement, and in cells. MPA reduced total cellular protein levels, consistent with an anti-metabolite effect without increased cytopathic activity. BKV infection was associated with a transient, significant reduction of collagen 1A1 on day 7 but not on days 14, 21, and 28 or in the presence of MPA. Reduction of alpha smooth muscle actin mRNA was observed only in the BKV + MPA group, and only on day 7. There was no significant alteration of heat shock protein 47 or transforming growth factor-β mRNA expression. These in vitro data suggest that MPA may have a protective, anti-viral effect in BKV-infected renal tubular cells with an anti-viral response. Maintaining, or even increasing, the MPA dose should be evaluated for reduction of BKV viremia levels.