Bin He |
 Associate Professor Ph.D., Purdue University, 1993 Room:8035 COMRB, Tel: 312-996-4986 Email: tshuo@uic.edu |
Major research interests in my laboratory focus on the viral response to cellular antiviral defenses. Current efforts are directed towards the g134.5 protein of herpes simplex viruses (HSV), a viral factor that blocks host antiviral defense mediated by the interferon induced double-stranded RNA-dependent protein kinase (PKR). Our long-term goal is to identify components involved in virus-host interaction and define their roles in viral pathogenesis. The g134.5 protein of HSV plays a key role in viral pathogenesis. This protein contains 263 amino acids with a large amino-terminal domain, a swivel region of 3 amino acids repeats and a carboxyl-terminal domain. Mutants that fail to express the g134.5 protein are incapable of replicating in the central nervous system and causing diseases in vivo. In human cells infected with the g134.5 deletion mutants initiation of viral DNA synthesis triggers the activation of PKR in host cells that phosphorylates the a subunit of the translation initiation factor 2 (eIF-2a) and consequently shuts off total protein synthesis. This leads to the inhibition of viral replication. In HSV infected cells the g134.5 protein is required to prevent the shutoff of protein synthesis and this function maps to the carboxyl terminal domain. It is believed that the g g134.5 protein and protein phosphatase 1 (PP1), in association with additional components, form a functional multi-protein complex that dephosphorylates eIF-2a and prevents shutoff of protein synthesis. Thus, unlike other human viruses, HSV appears to use a novel strategy to escape host antiviral response. One aspect of our research is to study (1) the structure and function of the g134.5 protein, (2) the molecular nature of interactions between eIF-2a, the g134.5 protein and protein phosphatase 1 and (3) the role of protein phosphatase 1 in viral pathogenesis in vivo. These studies should provide insights into HSV infection that could result in the development of novel therapeutic agents. It is significant that the carboxyl terminal domain of the g134.5 protein is homologous to the corresponding domain of a set of cellular protein known as GADD34/MyD116, which is expressed under conditions of DNA damage, growth arrest, apoptosis, and differentiation. Interestingly, substitution of the carboxyl terminus of the g134.5 protein with that of GADD34/MyD116 blocks PKR mediated translation shutoff in virus infected cells, suggesting that GADD34/MyD116 may perform a similar function. The cellular function of GADD34/MyD116 is unknown but is thought to be involved in apoptosis. In a second aspect of our research, we are studying the functions of GADD34 in viral infection and in cellular stress response. |
