Whereas herpes simplex virus 1 (HSV-1) transcription is restricted in latently infected neurons, where the genomes are mostly in silenced chromatin, all viral genes are transcribed in lytically infected cells, in which the genomes are dynamically chromatinized. Chromatinization may be a cellular defense to silence HSV-1, which would be counteracted by the viral transcription activators resulting in the highly dynamic viral chromatin. Although epigenetic regulation affects HSV-1 transcription during lytic infections, latency, and reactivation, the precise mechanisms are not entirely clear. Nucleosomes are dynamic; they slide, breathe, assemble and disassemble. These dynamics are affected by the histone variants and several posttranslational modifications. We and others have proposed that the most dynamic HSV-1 chromatin is transcriptionally competent whereas the least dynamic is silenced. However, the mechanisms yielding the unusually highly dynamic viral chromatin remain unknown.Several core histone variants such as macroH2A and H2A.B affect nucleosome dynamics and macroH2A is detected in HSV-1 chromatin. H2A.B assembles the most dynamic nucleosomes of any H2A variant and is the most dynamic core histone. H2A.B is typically enriched in highly transcribed cellular loci, whereas macroH2A assembles the least dynamic nucleosomes and is typically enriched in transcriptionally repressed chromatin. Whereas H2A, H2A.X and macroH2A had increased dynamics in infected cells, H2A.B dynamics decreased. H2A.B dynamics decreasedin infected cells is consistent with a larger fraction spending more time assembled into chromatin with the novel binding sites provided by HSV-1 DNA. In this work I constructed stably transduced HeLa cells expressing flag-tagged histone H2A, H2A.B, macroH2A, or H2B, which assembles the H2A/H2B nucleosome dimers with all H2A variants. I found that HSV-1 lytic chromatin is enriched in histone variant H2A.B, which is associated with highly dynamic and transcriptionally competent chromatin. Furthermore, histone H2A variants, as well as ectopic and endogenous H2B, were assembled into HSV-1 chromatin evenly throughout the HSV-1 genome, regardless of dynamics or transcriptional state. All histone H2A variants were evenly distributed through the viral genome together with H2B, indicating that the differences between the enrichment in the different variants relate to their differential assembly in H2A/H2B containing nucleosomes. When viral transcription was restricted, however, H2A.B became as depleted from the viral chromatin as H2A, whereas macroH2A became relatively enriched. I propose that lytic HSV-1 nucleosomes are relatively enriched in the dynamic variant H2A.B/H2B dimers to promote HSV-1 chromatin dynamics and global HSV-1 transcriptional competency, but this enrichment is lost when transcription is restricted to only the IE loci, most of the genome is not transcriptionally competent, and most genomes are in less dynamic chromatin. The results of this dissertation provide new information that leads to a better understanding of the nature of lytic HSV-1 chromatin dynamics, and it helps to unravel the mechanisms of the switch between the lytic and latent HSV-1 chromatin.