The Ends Dictate the Means: Promoter Switching in Herpesvirus Gene Expression

Abstract

Herpesvirus gene expression is dynamic and complex, with distinct complements of viral genes expressed at specific times in different infection contexts. These complex patterns of viral gene expression arise in part from the integration of multiple cellular and viral signals that affect the transcription of viral genes. The use of alternative promoters provides an increased level of control, allowing different promoters to direct the transcription of the same gene in response to distinct temporal and contextual cues. While once considered rare, herpesvirus alternative promoter usage was recently found to be far more pervasive and impactful than previously thought. Here we review several examples of promoter switching in herpesviruses and discuss the functional consequences on the transcriptional and post-transcriptional regulation of viral gene expression. Expected final online publication date for the Annual Review of Virology, Volume 8 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Long-read transcriptomics of Ostreid herpesvirus 1 uncovers a conserved expression strategy for the capsid maturation module and pinpoints a mechanism for evasion of the ADAR-based antiviral defence

“…Indeed, we confirm the complexity and high coding density of the OsHV-1 genome, with 274 transcripts grouped into 78 gene units, with evidence of polycistronic transcripts and multiple isoforms involving most of the genes. The high transcriptional complexity has been reported for several representatives of the order Herpesvirales (27), making proteomic and/or ribosome profiling data necessary to further investigate the true coding potential of these viruses (28). Our proteomics analysis supported only a small number of OsHV-1 proteins, most of them linked to important viral functions, such as virion formation and genome replication (e.g., the MCP, capsid maturation protease and DNA polymerase) or proteins that, despite having unknown function, were reported as highly expressed in other transcriptomic (13) or proteomic surveys performed in C. gigas infected with OsHV-1, such as ORF22 (29).…”

“…for several representatives of the order Herpesvirales (27), making proteomic and/or ribosome profiling data necessary to further investigate the true coding potential of these viruses (28).…”

The human cytomegalovirus decathlon: Ten critical replication events provide opportunities for restriction

“…The authors used these data to suggest 7 temporal expression classes (Rozman et al, 2022). Different isoforms also show different mechanisms of regulation at early and late times [reviewed (Hale and Moorman, 2021)]. UL44 is a prominent example as it is expressed early (Leach and Mocarski, 1989), but peak transcript and protein levels are reached late (Weekes et al, 2014;Rozman et al, 2022).…”

Chromatin control of human cytomegalovirus infection

“…To this end, reactivation is often experimentally induced in model systems by treating cells with small molecules (e.g., retinoic acid), cytokines, or phorbol esters, all of which trigger many of the same epigenetic changes and recruitment of epigenetic modifiers observed during lytic infection of permissive cells ( 137 , 140 , 141 ). While this provides insight into reactivation, these data must be taken in context, as distinct reactivation cues can lead to different promoter expression profiles within the same cell type or differentiation-driven activation of promoters across various cell types ( 33 , 34 , 142 ). For instance, treatment of THP-1 or Kasumi-3 cells with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA or PMA), leads to transcription predominantly from the intronic promoter, iP2 ( 34 , 143 , 144 ).…”