Kaposi's sarcoma-associated herpesvirus encodes several genes with sequence homology to cellular interferon regulatory factors. Among these, vIRF2 encoded by ORF K11.1 (short form) or K11 (full-length) participates in caspase-3-mediated inactivation of cellular IRF3 and slightly inhibits caspase-3 activity. Here, we have demonstrated that vIRF2 attenuates the transcriptional activity of forkhead box O3A protein via activation of the PI3K/Akt phosphatidylinositol 3-kinase/Akt pathway, inhibiting FOXO3A-mediated caspase-3 cleavage. Based on the collective findings, we suggest that vIRF2 acts as an activator in PI3K/Akt pathway. (C) 2016 Elsevier Inc. All rights reserved.