Zhangfei: a second cellular protein interacts with herpes simplex virus accessory factor HCF in a manner similar to Luman and VP16

Host cell factor (HCF, C1,VCAF or CFF) is a cellular protein that is requir ed for transcription activation of herpes simplex virus (HSV) immediate-ear ly (IE) genes by the virion protein VP16. The biological function of HCF re mains unclear. Recently we identified a cellular transcription activator, L uman. As with VP16, the transactivation function of Luman is also regulated by HCF. Here we report a second human protein, Zhangfei (ZF) that interact s with HCF in a fashion similar to Luman and VP16. Although ZF shares no si gnificant sequence homology with Luman, the two proteins have some structur al similarities. These include: a basic domain-leucine zipper (bZIP) region , an acidic activation domain and a consensus HCF-binding motif. Unlike Lum an, or most other bZIP proteins, ZF by itself did not appear to bind consen sus bZIP-binding sites. It was also unable to activate promoters containing these response elements. Although in transient expression assays ectopical ly expressed ZF was unable to block transactivation by VP16 of a HSV IE pro moter, ZF could prevent the expression of several HSV proteins in cells inf ected with the virus. The ability of ZF to block the synthesis of the HSV I E protein ICPO relied on its binding to HCF, since a mutant of ZF that was unable to bind HCF was also unable to prevent viral IE protein expression.