| During productive Herpes simplex virus type 1 (HSV-1) infection, the first viral proteins to be expressed are encoded by the immediate-early genes (68). One of these proteins, infected cell protein 27 (ICP27), is a key regulatory protein that exerts its effects mainly at the post-transcriptional level through interactions with itself, viral, and cellular proteins. ICP27 has been shown to interact with itself in the form of multimers, as well as with the viral protein ICP8 (94, 141). ICP27 also interacts with the following cellular proteins: SR proteins, SR protein kinase 1 (SRPK1), spliceosome-associated protein 145 (SAP 145), splicing associated factor p32 (p32), casein kinase 2 (CK2), heterogeneous nuclear ribonucleoprotein K (hnRNP K), the RNA export adaptor protein Aly/REF, the mRNA export receptor TAP/Nuclear Export Factor 1 (NXF-1), RNA polymerase II (RNAP II), Hsc70, poly A binding protein (PABP), eukaryotic initiation factor 3 (eIF3), and eukaryotic initiation factor 4G (eIF4G) (7-10, 17, 18, 29, 38, 117, 136, 142). The domains necessary for the protein-protein interactions of ICP27 have been mapped by mutational analysis to the N- and C-termini. Furthermore, the results from mutational analysis showed a number of proteins like RNAP II, Hsc70, and TAP/NXF-1 require both the N- and C-termini of ICP27 for their interactions (17, 29, 96, 136). Here, we show that head to tail intramolecular interaction between the N- and C-termini of ICP27 occurs and this association is important for interaction with the cellular RNA export receptor TAP/NXF1. Thus far, ICP27 has been shown to interact with a myriad of proteins, in vitro, yet we have little insight into the interaction dynamics of ICP27 in vivo. This is because experiments used to detect the ICP27-protein interactions were performed using static methods. Therefore, our studies give new insight into the in vivo associations of ICP27 as they change throughout the course of infection. |
