HSV1 latent transcription and non-coding RNA: A critical retrospective

Virologists have invested great effort into understanding how the herpes simplex viruses and their relatives are maintained dormant over the lifespan of their host while maintaining the poise to remobilize on sporadic occasions. Piece by piece, our field has defined the tissues in play (the sensory ganglia), the transcriptional units (the latency-associated transcripts), and the responsive genomic region (the long repeats of the viral genomes). With time, the observed complexity of these features has compounded, and the totality of viral factors regulating latency are less obvious. In this review, we compose a comprehensive picture of the viral genetic elements suspected to be relevant to herpes simplex virus 1 (HSV1) latent transcription by conducting a critical analysis of about three decades of research. We describe these studies, which largely involved mutational analysis of the notable latency-associated transcripts (LATs), and more recently a series of viral miRNAs. We also intend to draw attention to the many other less characterized non-coding RNAs, and perhaps coding RNAs, that may be important for consideration when trying to disentangle the multitude of phenotypes of the many genetic modifications introduced into recombinant HSV1 strains.