Mycophenolic acid inhibits replication of Type 2 Winnipeg, a cerebrospinal fluid-derived reovirus isolate

Abstract

BACKGROUND: The role of reoviruses in human disease is uncertain. Most identified cases are sporadic and asymptomatic or produce minor upper respiratory or gastrointestinal symptoms. In November 1997, a reovirus was isolated from the cerebrospinal fluid of a severe combined immune deficient infant in Winnipeg, Manitoba. RNA characterization and sequencing studies demonstrated this reovirus isolate to be unique. Thus, the virus was named Type 2 Winnipeg (T2W). OBJECTIVES: Mycophenolic acid (MPA), a drug primarily used as an immunosuppressive agent, was assessed in the capacity to inhibit T2W viral growth. METHODS: The effects of MPA on viral growth were determined by plaque reduction assays. Cells were treated with different MPA concentrations, infected with T2W and incubated at 37°C for 0 h to 72 h. Virus titres were determined and compared with untreated controls. RESULTS: Production of infectious T2W progeny decreased more than 99% at 3 μg/mL MPA compared with untreated controls. Inhibition was not caused by cell toxicity because there was no difference in cell viability. The 50% cell toxic dose was 30 μg/mL MPA. CONCLUSIONS: MPA was able to inhibit viral growth of the novel reovirus T2W. Although MPA is usually used as an immunosuppressive agent, and despite the fact that T2W was isolated from an immunocompromised patient, these results suggest that MPA could have been used as a possible treatment at subimmunosuppressive doses. Animal studies to better define the antiviral and immunosuppressive activities of MPA (and its prodrug mycophenolate mofetil) appear warranted.