Herpes simplex virus transactivator VP16 discriminates between HCF-1 and anovel family member, HCF-2

Herpes simplex virus infection is initiated by VP16, a viral transcription factor that activates the viral immediate-early (IE) genes. VP16 does not r ecognize the IE gene promoters directly but instead forms a multiprotein co mplex with Oct-1 and HCF-1, a ubiquitous nuclear protein required for progr ession through the G(1) phase of the cell cycle. The functional significanc e of recruiting HCF-1 to the VP16-induced complex is not understood, Here w e describe the identification of a second HCF-like protein, designated HCF- 2, HCF-2 is smaller than HCF-1 but shares three regions of strong amino aci d sequence homology, including the beta-propeller domain required for assoc iation with VP16. HCF-2 is expressed in many tissues, especially the testis , and shows a more dynamic pattern of subcellular localization than HCF-1. Although HCF-2 associates with VP16 and can support complex assembly with O ct-1 and DNA, it is significantly less efficient than HCF-1. A similar pref erence is shown by LZIP, a cellular counterpart of VP16. Analysis of chimer ic proteins showed that differences between the fifth and sixth kelch repea ts of the beta-propeller domains from HCF-1 and HCF-2 dictate this selectiv ity. These results reveal an unexpected level of specificity in the recruit ment of HCF-1 to the VP16-induced complex, paralleling the preferential sel ection of Oct-1 rather than the closely related POU domain protein Oct-2, I mplications for regulation of the viral life cycle are discussed.