Selected elements of herpes simplex virus accessory factor HCF are highly conserved in Caenorhabditis elegans

HCF is a mammalian nuclear protein that undergoes proteolytic processing an d is required for cell proliferation. During productive herpes simplex viru s (HSV) infection, the viral transactivator VP16 associates with HCF to ini tiate HSV gene transcription. Here, we show that the worm Caenorhabditis el egans possesses a functional homolog of mammalian HCF that can associate wi th and activate the viral protein VP16. The pattern of sequence conservatio n, however, is uneven. Sequences required for mammalian HCF processing are not present in C. elegans HCF. Furthermore, not all elements of mammalian H CF that are required for promoting cell proliferation are conserved. Nevert heless, unexpectedly, C. elegans HCF can promote mammalian cell proliferati on because a region of HCF that is conserved can promote mammalian cell pro liferation better than its human counterpart. These results suggest that HC F possesses a highly conserved role in metazoan cell proliferation which is targeted by VP16 to regulate HSV infection. The precise mechanisms, howeve r, by which HCF functions in mammals and worms appear to differ.