Deep splicing plasticity of the human adenovirus type 5 transcriptome drives virus evolution

Research output: Contribution to journalArticlepeer-review


  • I’ah Donovan-Banfield
  • Andrew Turnell
  • Julian Hiscox
  • Keith Leppard
  • David Matthews

Colleges, School and Institutes


Viral genomes have high gene densities and complex transcription strategies rendering transcriptome analysis through short-read RNA-seq approaches problematic. Adenovirus transcription and splicing is especially complex. We used long-read direct RNA sequencing to study adenovirus transcription and splicing during infection. This revealed a previously unappreciated complexity of alternative splicing and potential for secondary initiating codon usage. Moreover, we find that most viral transcripts tend to shorten polyadenylation lengths as infection progresses. Development of an open reading frame centric bioinformatics analysis pipeline provided a deeper quantitative and qualitative understanding of adenovirus’s genetic potential. Across the viral genome adenovirus makes multiple distinctly spliced transcripts that code for the same protein. Over 11,000 different splicing patterns were recorded across the viral genome, most occurring at low levels. This low-level use of alternative splicing patterns potentially enables the virus to maximise its coding potential over evolutionary timescales


Original languageEnglish
Article number124
Number of pages14
JournalCommunications Biology
Issue number1
Publication statusPublished - 13 Mar 2020


  • adenovirus, transcriptomics