Stabilization but not the transcriptional activity of herpes simplex virusVP16-induced complexes is evolutionarily conserved among HCF family members

The human herpes simplex virus (HSV) protein VP16 induces formation of a tr anscriptional regulatory complex with two cellular factors-the POU homeodom ain transcription factor Oct-1 and the cell proliferation factor HCF-1-to a ctivate viral immediate-early-gene transcription. Although the cellular rol e of Oct-1 in transcription is relatively well understood, the cellular rol e of HCF-1 in cell proliferation is enigmatic. HCF-1 and the related protei n HCF-2 form an HCF protein family in humans that is related to a Caenorhab ditis elegans homolog called CeHCF. In this study, we show that all three p roteins can promote VP16-induced-complex formation, indicating that VP16 ta rgets a highly conserved function of HCF proteins. The resulting VP16-induc ed complexes, however, display different transcriptional activities. In con trast to HCF-1 and CeHCF, HCF-2 fails to support VP16 activation of transcr iption effectively. These results suggest that, along with HCF-1, HCF-2 cou ld have a role, albeit probably a different role, in HSV infection. CeHCF c an mimic HCF-1 for both association with viral and cellular proteins and tr anscriptional activation, suggesting that the function(s) of HCF-1 targeted by VP16 has been highly conserved throughout metazoan evolution.