Herpes simplex virus type 1 (HSV-1) is a DNA virus with complicated genomic structures and has three types of genes that are under strict temporal expression. They are divided into immediate-early (α), immediate-early (β), and late (γ) genes (5). The α gene encode proteins that have essential functions in transcriptional activation and inhibition along with multiple regulatory and control processes of viral genes expressed at later times in infection (22). Meanwhile, as a result of interacting with host proteins (12), ICPs are most likely to control virus/cell interactions in terms of not only lytic infection, but also the establishment of viral latency in neuronal cells (19). It has been reported that the expression of some infected cell proteins (ICPs) in neuronal cells is apparently suppressed as a result of entry into HSV-1 viral latency (2). In contrast, a few studies have demonstrated that some ICPs expressed in neuronal cells did not activate the transcription of β and γ genes when regulated by factors within neuronal cells (25). No further investigations were conducted to verify either of these two hypotheses. It has been demonstrated that ICP0 and ICP22 might either activate or suppress transcription of viral genes at different phases via interactions with the transcri-ptional and regulatory systems (21). However, this interaction requires further confirmation in the neuronal cellular environment due to the specific biological properties of neuronal cells. As a consequence, a study was designed to investigate possible mechanisms in HSV-1 infected neuronal cells by characterizing neuroblastoma cells (1). This approach provides a novel approach in the study of this area. In cellular biology neuronal cells are end cells with specific functions, but lack a transcriptional and regulatory system for proliferation (24); unlike in other cells, this system has essential multifunctional structures, such as a promyelocytic leukaemia-nuclear body (PML-NB) etc. (3, 20), which has been shown to be associated with some ICP proteins in HSV-1 studies. All of these implications have provided evidence on the functions of HSV-1 ICPs in neuronal cells. More strikingly, the study of neuroblastoma cells prior to their proliferation has offered a potential model that requires further investigation. In this preliminary report, the expression, localization and possible potential interactive functions of HSV-1 ICP0, ICP22, and ICP27 in neuroblastoma cells (SH-SY5Y strain) were investigated based upon the above evidence. The generated data are discussed.
Biological Analysis of HSV-1 Immediate-early Proteins ICP0, ICP22, and ICP27 in Neuroblastoma Cells
- Received Date: 29 January 2008
- Accepted Date: 10 June 2008
Abstract: The three immediate-early proteins of HSV-1, ICP0, ICP22, and ICP27, have specific and pivotal functions in transcriptional activation and inhibition, multiple regulatory and control processes of viral genes. In this paper, the expression and localization of these three proteins were studied in neuroblastoma cells using biochemical assays, and their possible and potential interactive functions are discussed. The data show that the three proteins are localized in different structures, specifically in the PML-NB-associated structure, which is a specific nuclear structure composed of many protein molecules and bound tightly to the nuclear matrix in neuroblastoma cells. The results suggest that the activating and suppressive functions of ICPs are mostly dependent on their transcriptional and regulatory roles, including the PML-NB-associated structure.