Earlier studies have shown that the DNA of herpes simplex virus 1 consists of two covalently linked components, L and S, each flanked by inverted repeats. (A) Regions of repressed (heterochromatin) and permissive (euchromatin) chromatin juxtaposed within the HSV-1 genome. In this study, we show that histone occupancy on the viral genome gradually increased with time when transcription of the viral immediate-early (IE) genes was inhibited either by deletion of the VP16 activation domain or by chemical inhibition of RNA polymerase II (RNAP II). Both p53RE-L and p53RE-S are capable of conferring p53-dependent transcriptional activation onto a heterologous reporter gene. Molecular combing analysis was performed on DNA extracted from viral particles and BSR, Vero, COS-7, and Neuro-2a cells infected with either strain SC16 or KOS of HSV-1, as well as from tissues of experimentally infected mice. Labeling of HSV-1 DNA detected by a viral DNA probe revealed that non-encapsidated viral genomes were present exclusively within this centrally located viral region whereas encapsidated HSV-1 genomes, which were more widely distributed in the infected cell, were seen within the marginated host chromatin as well as the central viral region. The human alphaherpesvirus herpes simplex virus 1 (HSV-1), infects sensory neurons, where it establishes a lifelong latent infection as a circular episome associated with histones (6, 16, 38, 40, 44).
This work, presents the first evidence of extended G-quadruplex sites in key regions of the HSV-1 genome, indicates the possibility to block viral DNA replication by G-quadruplex-ligand and therefore provides a proof of concept for the use of G-quadruplex ligands as new anti-herpetic therapeutic options. While the majority of the viral genome became relatively quiescent, the latency-associated transcript was specifically upregulated. The results suggest that this population arose by recombination through a directly repeated sequence inserted in place of the deleted L-S junction. Both p53RE-L and p53RE-S are capable of conferring p53-dependent transcriptional activation onto a heterologous reporter gene. The Tudor protein survival motor neuron (SMN) is a chromatin-binding protein that interacts with methylated lysine 79 of histone H3 Sabra M., Texier P., El Maalouf J., and Lomonte P. This barrier can be overcome by activator-mediated recruitment of transcriptional coactivators that either covalently modify histones (29, 41) or remodel the position of nucleosomes along DNA (11, 56). © 2014 Elsevier Inc.