Viral Decoys: The Only Two Herpesviruses Infecting Invertebrates Evolved Different Transcriptional Strategies to Deflect Post-Transcriptional Editing

Abstract

The highly versatile group of Herpesviruses cause disease in a wide range of hosts. In invertebrates, only two herpesviruses are known: the malacoherpesviruses HaHV-1 and OsHV-1 infecting gastropods and bivalves, respectively. To understand viral transcript architecture and diversity we first reconstructed full-length viral genomes of HaHV-1 infecting Haliotis diversicolor supertexta and OsHV-1 infecting Scapharca broughtonii by DNA-seq. We then used RNA-seq over the time-course of experimental infections to establish viral transcriptional dynamics, followed by PacBio long-read sequencing of full-length transcripts to untangle viral transcript architectures at two selected time points. Despite similarities in genome structure, in the number of genes and in the diverse transcriptomic architectures, we measured a ten-fold higher transcript variability in HaHV-1, with more extended antisense gene transcription. Transcriptional dynamics also appeared different, both in timing and expression trends. Both viruses were heavily affected by post-transcriptional modifications performed by ADAR1 affecting sense-antisense gene pairs forming dsRNAs. However, OsHV-1 concentrated these modifications in a few genomic hotspots, whereas HaHV-1 diluted ADAR1 impact by elongated and polycistronic transcripts distributed over its whole genome. These transcriptional strategies might thus provide alternative potential roles for sense-antisense transcription in viral transcriptomes to evade the host’s immune response in different virus–host combinations.

ADAR-Editing during Ostreid Herpesvirus 1 Infection in Crassostrea gigas : Facts and Limitations

“…By tracing ADAR hyper-editing along OsHV-1 infection in C. gigas , we demonstrated that in the early stage of infection host RNAs are more impacted than viral RNAs, with viral-directed editing increasing along the time course and suggesting that at later stages ADAR1 will mostly target viral dsRNAs. This increase is in agreement with data reported demonstrated for OsHV-1 infection in S. broughtonii ( 9 ), and likely mirrors the different abundances of viral and host dsRNAs during infection, with the latter increasing as a consequence of sense–antisense gene pair cotranscription ( 9 ). Next, we showed that host hyper-editing levels varied along each experiment.…”

“…This likely indicates that OsHV-1 resistant and immuno-primed oysters are trained/prone for hyper-editing, even at early stages of infection. Differently, non-IP oysters rapidly reached the same hyper-editing levels of IP oysters at 12 hpi, suggesting that OsHV-1 is highly effective in stimulating hyper-editing, probably because of its peculiar transcriptional architectures ( 9 ). A considerable fraction of the oyster transcriptome (∼0.5%) was hyper-edited irrespective of the experiment or condition.…”

“…Moreover, distinct transcriptional profiles characterized the antiviral response of oyster families showing differential susceptibility to OsHV-1, with the resistant oysters displaying a higher basal expression of antiviral genes and a possible quicker transcriptional response ( 8 ). Even the viral transcriptome architecture emerges as a possible determinant of host–pathogen interactions, since PacBio RNA data revealed nested gene isoforms, polycistronic genes, and abundant natural antisense transcripts (NATs) in OsHV-1 and HaHV-1, possibly attracting RNA editing activity ( 9 ). Adenosine-to-inosine (A-to-I) editing mediated by enzymes of the Adenosine Deaminase Acting on dsRNA (ADAR) family, produce posttranscriptional conversions in RNAs with double-stranded structures ( 10 ), a phenomenon relevant in natural and experimental viral infections ( 11 ).…”

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

“…OsHV-1 transcriptome map based on PacBio long reads (21). Moreover, our data illuminates interesting new aspects of the OsHV-1 transcription beyond the mere expression analysis.…”

“…specific miRNAs or transcripts ( 42)), whereas in malacoherpesvirus, RNA editing extensively impacted multiple transcripts. We previously showed that in OsHV-1, the RNA editing is concentrated within genomic hotspots, whereas in HaHV-1 these modifications are more evenly distributed across the genome (21). However, up to now, the extension of RNA editing was indirectly deduced tracing highly modified short reads, as a proxy of ADAR hyper-editing, whereas no approaches were undertaken to detect inosines.…”