Virus-induced FoxO factor facilitates replication of human cytomegalovirus.

Recently, it was reported that the forkhead box O (FoxO) transcription factor promotes human cytomegalovirus (HCMV) replication via direct binding to the promoters of the major immediate-early (MIE) genes, but how the FoxO factor impacts HCMV replication remains unknown. Here, it is reported that FoxO1 expression is strongly induced by HCMV infection in cells of fibroblast origin. Suppression of the FoxO1 gene by specific RNA interference significantly inhibited HCMV growth and replication, but viral DNA synthesis was not affected considerably. Interestingly, depletion or overexpression of FoxO1 had a significant effect on the expression of viral early/late transcripts. FoxO1 was found to colocalize with the pUL44 protein subunit of viral replication compartments without direct association with DNA. This study highlights how FoxO enhances HCMV gene transcription and viral replication to promote infection.