Upon lytic infection of permissive cells, the herpes simplex virus (HS
V) transactivator protein VP16 associates with an accessory protein te
rmed host cell factor (HCF). Binding to HCF activates VP16 for associa
tion with the octamer motif-binding protein Oct-1, to form a multiprot
ein-DNA complex responsible for activating transcription of the HSV im
mediate early genes. We show that HCF comprises a series of related po
lypeptides that range from 110 to 300 kd, all of which are encoded by
a single gene. Although there is no obvious sequence similarity betwee
n HCF and other known proteins, HCF contains eight repeats of a new 26
amino acid motif. cDNAs encoding HCF predict a large open reading fra
me of 2035 codons. When expressed in human cells, this large open read
ing frame encodes both the 300 kd and smaller HCF polypeptides, indica
ting that the smaller polypeptides arise by processing of the 300 kd p
rotein.