Optimal Gene Expression for Efficient Replication of Herpes Simplex Virus Type 1 (HSV-1)

Abstract

Herpesviridae is a large class of animal viruses. Herpes simplex virus type 1 (HSV-1) is a prototypic virus in this taxonomic group. HSV-1 belongs to the Alphaherpesviridae which are most frequently responsible for cold-sore lesions around the lips and mouth. HSV-1 is extensively studied not only as a causative agent of human disease but also as a general model system for the gene expression. In the lytic replication cycle of HSV-1, temporally ordered viral gene expression is typically observed, that is, immediate early, early and late gene (Boehmer & Lehman, 1997; Boehmer & Nimonkar, 2003) . This classification of viral gene is based on the expression timing from the start of the infection. The immediate early gene is expressed within 30 minutes from the infection. The expression of the immediate early gene is introduced by the cooperation between the host transcription factor and VP-16 which is packed in the tegmentum of HSV-1 particle. The protein complex, composed of the host transcription factor and VP-16, binds to the immediate early gene promoter and then activates the immediate early gene expression (Wysocka & Herr, 2003). Immediate early genes encode the transcription factors. Under the control of the immediate early gene products, other viral genes are expressed (Weir, 2001; Yamamoto et al., 2006). 2~3 hours after infection, the early gene is expressed, delayed from the immediate early gene and proceeding to the late gene. Finally, the late gene expression has started after 8 hours after infection. Both the early and the late gene expression are regulated by the immediate early gene products such as ICP4 (Kim et al., 2002). The difference of the expression timing between the early and late gene is caused by the structural difference of the early and the late gene promoter as shown in Fig.1. In the early gene promoter, many binding sites to the immediate early gene products are tandemly repeated. On the other hand, the number of repeat binding sites in the late gene promoter is fewer than that in the early gene promoter. The binding affinity of the early gene promoter to the immediate early gene products is higher as compared with the late gene promoter. Therefore the expression of the early gene proceeds to that of the late gene. The mechanism regulating the temporally ordered viral gene expression of HSV-1 is clarified as mentioned above. But the function of this expression pattern is not clear yet. The functional meaning of the expression profile of the HSV-1 gene is theoretically studied (Nakabayashi & Sasaki, 2009). In this chapter, the function of the