Short CommunicationPersistent infection of human pancreatic cells with Coxsackievirus B4 is cured by fluoxetine

- The antiviral activity of fluoxetine against CVB4 has been displayed.
- Fluoxetine does not inhibit the viral particle before entry into the cell.
- Fluoxetine can cure persistent CVB4 infection in human pancreatic cells.

Group B Coxsackieviruses (CVB) are involved in various acute clinical features and they can play a role in the development of chronic diseases like type 1 diabetes. The persistence of CVB has been described in vitro and in vivo in various models. Fluoxetine was reported to inhibit the replication of CVB1-3, which prompted us to study the in vitro antiviral activity of fluoxetine against CVB4 in models of acute infection. In addition we took advantage of a chronically CVB4-infected Panc-1 cell line to evaluate the antiviral effect of fluoxetine in a model of persistent CVB4 infection.An inhibition of the CVB4 replication was obtained when fluoxetine was added at 5.48 μM to Hep-2 cell cultures. No inhibitory effect was observed when CVB4 was mixed with fluoxetine for 2 h and filtered to eliminate fluoxetine before inoculation to cells, or when cells were treated up to 96 h and washed before viral inoculation. Fluoxetine (5.48 μM) reduced viral replication by more than 50% in acutely infected Panc-1 cell cultures. A dramatic decrease of infectious particles levels in supernatants of Panc-1 cells chronically infected with CVB4 was obtained a few days after treatment with fluoxetine and no infectious viral particle was found as soon as day 21 of treatment, and intracellular enteroviral RNA was undetectable by RT-PCR after three weeks of treatment.These data display that fluoxetine can inhibit the replication of CVB4 and can cure Panc-1 cells chronically infected with CVB4.