LAT

LATs are approximately 8.3 kb long non-coding RNA expressed in the nucleus of latently infected cells (Cabrera JR et al. 2018). Sensory neurons harboring the virus contain nuclear (LATs) responsible for modifying the chromatins of the viral genome, resulting in stable but reversible silencing of the HSV genome. Under latent conditions, LATs remain highly expressed and suppress the expression of immediate early (IE) genes, which are among the most important genes in the lytic cycle (Cabrera JR et al. 2018). LATs thus play a role in protecting latently infected neurons from apoptosis through the epigenetic modification of histones (Perng GC et al.2000).

Herpes simplex virus 1 (HSV-1) causes a lifelong latent infection in sensory neurons during which viral lytic gene expression is suppressed. The only highly expressed viral gene product during latent infection is the latency-associated transcript (LAT), a non-protein-coding RNA that is strongly involved in the epigenetic regulation of HSV-1 gene expression. Whether LATs enhances reactivation through a direct effect on the reactivation process or whether it increases the establishment of latency and thereby makes more latently infected neurons available for reactivation is not yet clear. In animal experiments, LAT-negative mutants appear to establish latency in fewer neurons than wild-type HSV-1.

1. Cabrera JR et al. (2018) Neuronal Subtype Determines Herpes Simplex Virus 1 Latency-Associated-Transcript Promoter Activity during Latency. J Virol 92:e00430-18.
2. Nicoll MP et al. (2016) The HSV-1 Latency-Associated Transcript Functions to Repress Latent Phase Lytic Gene Expression and Suppress Virus Reactivation from Latently Infected Neurons. PLoS Pathog 12:e1005539.