Selected Elements of Herpes Simplex Virus Accessory Factor HCF Are Highly Conserved in Caenorhabditis elegans

Abstract

HCF is a mammalian nuclear protein that undergoes proteolytic processing and is required for cell proliferation. During productive herpes simplex virus (HSV) infection, the viral transactivator VP16 associates with HCF to initiate HSV gene transcription. Here, we show that the worm Caenorhabditis elegans possesses a functional homolog of mammalian HCF that can associate with and activate the viral protein VP16. The pattern of sequence conservation, however, is uneven. Sequences required for mammalian HCF processing are not present in C. elegans HCF. Furthermore, not all elements of mammalian HCF that are required for promoting cell proliferation are conserved. Nevertheless, unexpectedly, C. elegans HCF can promote mammalian cell proliferation because a region of HCF that is conserved can promote mammalian cell proliferation better than its human counterpart. These results suggest that HCF possesses a highly conserved role in metazoan cell proliferation which is targeted by VP16 to regulate HSV infection. The precise mechanisms, however, by which HCF functions in mammals and worms appear to differ.

ACKNOWLEDGMENTS

We thank Richard Freiman, Loren Peña, and Angus Wilson for their involvement in the early phase of these studies; Serge Lichsteiner and Robert Tjian for a C. elegans extract; Deborah Aufiero for DNA sequencing; Robert Barstead for a C. elegans cDNA library; Georgia Binns for synthesis of the CeHCF_N16 peptide; James Duffy for graphic arts; and Michele Cleary, Nouria Hernandez, and William Tansey for critical readings of the manuscript.

M.O.H. is a Rita Allen Foundation Scholar. Y.L. was supported in part by PHS training grant CA09176. These studies were supported by PHS grant GM54598.