Fashionably late: Temporal regulation of HSV-1 late gene transcription
Joseph R. Heath, Jill A. Dembowski
Abstract
Herpes simplex virus type-1 (HSV-1) is an alpha herpesvirus that infects over 60% of the human population Infection results in a variety of disease manifestations, including cold sores, encephalitis, and keratitis. The HSV-1 genome contains approximately 152 kb of doublestranded DNA and includes over 80 genes Recently, studies using direct RNA sequencing, long-read sequencing, and ribosome profiling have revealed the transcriptional complexity of the HSV-1 genome and demonstrate that the genome actually contains over 200 open reading frames Viral genes are classified into 4 groups depending on their expression kinetics, including immediate early (), early (), leaky-late ( 1 ), and true late ( 2 ) genes. HSV-1 DNA replication is a key point in the infectious cycle, as it enables 2 and amplifies 1 transcription Below, we discuss the studies that defined the 4 HSV-1 gene classes and examine how viral DNA replication may facilitate a switch to regulate ( 1 / 2 ) gene transcription. Although the HSV-1 gene expression cascade was identified over 40 years ago, high-throughput sequencing approaches continue to reveal new insight into how each gene class is regulated