Prostratin exhibits both replication enhancing and inhibiting effects on FIV infection of feline CD4+ T-cells

The phorbol ester Prostratin may either stimulate or inhibit human immunodeficiency virus-1 (HIV-1) replication. Here we report that Prostratin also exhibits a similar dual action upon feline immunodeficiency virus (FIV) replication in an IL-2-dependent feline CD4+ T-cell line (MYA-1). While withdrawal of IL-2 halted FIV spread, Prostratin rescued virus production and cell viability, mimicking the functions of the cytokine. Conversely, FIV grew rapidly in the presence of IL-2 and this was inhibited by Prostratin. In contrast to HIV-1, Prostratin mediated inhibition of FIV through means other than blocking virus entry. Co-application of the protein kinase C (PKC) inhibitor Gö6850 with Prostratin reversed both the inhibitory and stimulatory effects, suggesting that PKC is crucial for FIV replication.

► Prostratin reactivates productive infection from FIV infected, IL-2-depleted feline CD4+ T-cells. ► When the infected cells were supplemented with IL-2, Prostratin inhibits productive infection with FIV. ► Dual action of Prostratin on FIV-infected cells mirrors the effect of the compound on human cells infected with HIV-1. ► Dual action of Prostratin on FIV is dependent on PKC. ► Prostratin's inhibitory effect on FIV is not due to a block at viral entry, contrary to results from HIV-1 studies.