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Herpes simplex virus Research
Animations of steps of HSV Infection and Replication
RNA Transcription During Productive Infection
The transcription of the HSV genome during productive infection occurs with cellular transcriptional machinery and viral promoters utilizing cellular transcription factor binding sites. Most viral transcripts are not spliced.
There are two main phases of transcription--early, which takes place prior to genome replication, and late, which takes place upon replicated genomes in virus replication compartments formed in the infected cell nucleus.
Early transcription is divided into two phases--immediate early and delayed early. Immediate early transcription takes place at five promoters immediately upon the viral genome's entering the nucleus. Here, virion-associated alpha-TIF binds to cellular Oct-1, which has bound to TAATGARAT sequences in enhancers upstream of the immediate early promoters. This results in efficient assembly of the pre-initiation complex at the TATA box and pol II-mediated transcription. Immediate-early transcripts are transported to the cytoplasm, translated, and the immediate-early proteins migrate back to the nucleus. All further transcription requires the action of these proteins, especially the alpha4 protein, which is a generalized transcription activator working by binding multiple sites on the genome and then interacting with nearby TATA boxes to facilitate assembly of pre-initiation complexes.
Early transcription proceeds and early proteins are translated in the cytoplasm, migrate back to the nucleus, and mediate the replication of the viral genome. As genomes replicate, they concentrate into discrete compartments and late transcription occurs there. Early transcription is not favored in these compartments and declines with genome replication.
Late transcripts also fall into two general groups, leaky-late and strict-late--these differ in the amount of transcription observed prior to genome replication. These are controlled by promoters that have different functional architectures, but which both have sequence elements downstream of the TATA box important in stabilizing the formation of pre-initiation complexes. Some strict late promoters contain an element (DAS for downstream activating sequence) that interacts with one or more cellular factors (DBF for DAS binding factor) to mediate the efficient formation of late transcription complexes.
Illustration and Flash animations by
Scientific, Medical and Veterinary Illustration.
The animations are available for download for classroom teaching.