In vitro effect of cyclosporin A on primary and chronic BK polyoma virus infection in Vero E6 cells

Abstract

Cyclosporin A (CsA) is known to possess antiviral activity against several viruses in vitro, but the effect of CsA on BK polyoma virus (BKV) replication has not been examined. We investigated the impact of CsA on primary, chronic, and high-level BKV infection using a cell system of kidney cell origin (Vero E6 cells). During the first 2 h post infection, cells treated with CsA up to 3200 microg/L showed a near-identical BK viral load to untreated cells, with only a very minor reduction in the CsA-treated cells observed at 4 h. In chronic culture, CsA completely suppressed the primary BKV infection peak in a non-dose-dependent manner within the dose range of 200-12,800 microg/L (P<0.05). BKV reactivation was also inhibited in the presence of CsA at doses of 200-3200 microg/L: the mean number of BKV DNA copies/mL remained stable or even decreased slightly compared with a 7-log increase in the non-CsA group (P<0.01). CsA did not influence BKV DNA copies/mL in Vero E6 cells with high-level infection (>10(9) copies/mL). Cellular protein measurements indicated that the antiviral effect of CsA was not a result of cytotoxicity. These findings from a relevant in vitro kidney cell system indicate that CsA suppresses the primary BKV infection peak and inhibits escape to BKV reactivation; these effects are dose independent and not related to cytotoxicity. The intracellular antiviral mode of action of CsA against BKV does not appear to be via inhibition of viral cell entry pathways.

A Suppressive Effect of Cyclosporine A on Replication and Noncoding Control Region Activation of Polyomavirus BK Virus

“…For example, Watashi et al (15) and Nakagawa et al (16) have demonstrated a suppressive effect of CsA on replication of hepatitis C virus (HCV). Recently, it has been discovered that CsA can also suppress BKV replication in green monkey kidney cells (Vero E6 cells) (17). Thus, investigating the effect of CsA on BKV replication in human kidney cells is warranted.…”

BK Virus Screening and Management Following Kidney Transplantation: An Update

“…Similar to registry data, results of the DIRECT study (in which de novo transplant recipients were randomized to receive either CSA or tacrolimus) revealed a lower incidence of BK viremia in CSAtreated patients compared with their tacrolimus-treated counterparts at 1-year (4.8% vs. 12.1%, p=0.004) [3]. In vitro studies suggest that CSA may exert an antiviral effect on BKV via suppression of viral replication [4,5] whereas tacrolimus has been reported to activate BKV replication in primary human tubular epithelial cells via the FK-binding protein 12 pathway [6]. Nonetheless, not all studies demonstrated a lower incidence of BK viremia with tacrolimus compared with CSA-treated patients [7].…”

Cyclosporin A Inhibits the Propagation of Influenza Virus by Interfering with a Late Event in the Virus Life Cycle

“…CsA reportedly inhibits the replication of various viruses such as human immunodeficiency virus type-1, hepatitis C virus, coronaviruses, vaccinia virus, vesicular stomatitis virus, herpes simplex virus, and BK polyomavirus (9)(10)(11)(12)(13)(14)(21)(22)(23)(24)(25)(26). CsA has antiviral effects on a wide range of viruses; therefore, we hypothesized that CsA would inhibit the multiplication of influenza virus.…”