The HSV-1 Latency-Associated Transcript Functions to Repress Latent Phase Lytic Gene Expression and Suppress Virus Reactivation from Latently Infected Neurons
| dc.cclicence | CC-BY-NC | en |
| dc.contributor.author | Hann, William | |
| dc.contributor.author | Shivkumar, Maitreyi | |
| dc.contributor.author | Connor, Viv | |
| dc.contributor.author | Efstathiou, Stacey | |
| dc.contributor.author | Nicoll, Michael P. | |
| dc.contributor.author | Harman, Laura E.R. | |
| dc.contributor.author | Coleman, Heather M. | |
| dc.contributor.author | Proenca, Joao T. | |
| dc.date.acceptance | 2016-03-10 | |
| dc.date.accessioned | 2019-10-10T14:30:24Z | |
| dc.date.available | 2019-10-10T14:30:24Z | |
| dc.date.issued | 2016-04-07 | |
| dc.description | open access article | en |
| dc.description.abstract | Herpes simplex virus 1 (HSV-1) establishes life-long latent infection within sensory neurons, during which viral lytic gene expression is silenced. The only highly expressed viral gene product during latent infection is the latency-associated transcript (LAT), a non-protein coding RNA that has been strongly implicated in the epigenetic regulation of HSV-1 gene expression. We have investigated LAT-mediated control of latent gene expression using chromatin immunoprecipitation analyses and LAT-negative viruses engineered to express firefly luciferase or β-galactosidase from a heterologous lytic promoter. Whilst we were unable to determine a significant effect of LAT expression upon heterochromatin enrichment on latent HSV-1 genomes, we show that reporter gene expression from latent HSV-1 genomes occurs at a greater frequency in the absence of LAT. Furthermore, using luciferase reporter viruses we have observed that HSV-1 gene expression decreases during long-term latent infection, with a most marked effect during LAT-negative virus infection. Finally, using a fluorescent mouse model of infection to isolate and culture single latently infected neurons, we also show that reactivation occurs at a greater frequency from cultures harbouring LAT-negative HSV-1. Together, our data suggest that the HSV-1 LAT RNA represses HSV-1 gene expression in small populations of neurons within the mouse TG, a phenomenon that directly impacts upon the frequency of reactivation and the maintenance of the transcriptionally active latent reservoir. | en |
| dc.exception.ref2021codes | 254a | en |
| dc.funder | MRC (Medical Research Council) | en |
| dc.identifier.citation | Nicoll, M.P., Hann, W., Shivkumar, M., Harman, L.E.R., Connor, V., Coleman, H.M., Proença, J.T., Efstathiou, S. (2016)The HSV1 Latency-Associated Transcript Functions to Repress Latent Phase Lytic Gene Expression and Suppress Virus Reactivation from Latently Infected Neurons. Pathogens,12(4),e1005539. | en |
| dc.identifier.doi | https://doi.org/10.1371/journal.ppat.1005539 | |
| dc.identifier.uri | https://dora.dmu.ac.uk/handle/2086/18608 | |
| dc.language.iso | en | en |
| dc.projectid | Grant MR/J00223 | en |
| dc.publisher | PLoS | en |
| dc.title | The HSV-1 Latency-Associated Transcript Functions to Repress Latent Phase Lytic Gene Expression and Suppress Virus Reactivation from Latently Infected Neurons | en |
| dc.type | Article | en |