Identification of a novel structural motif and overexpression of key transcripts elucidated in Adenovirus 10

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Abstract
Adenoviruses are widely used as vectors for subunit vaccines and oncolytic therapies. Efficient vectors must infect target cells and deliver therapeutic transgenes at high levels. Species D adenoviruses, such as human adenovirus type 10 (HAdV-D10), are promising candidates due to low seroprevalence in humans. Here, we present the cryo-electron microscopy structure of the HAdV-D10 capsid alongside transcriptomic profiling of infected cells to inform vector development. The fiber shaft, essential for cell entry, was resolved at 4.6 Å, revealing a previously uncharacterized ‘umbrella’ motif. Viral transcript analysis using an ORF-centric pipeline uncovered key differences from HAdV-C5, including abundant expression of a transcript encoding a protein equivalent to mature protein VII. These findings highlight the importance of detailed vector characterization prior to clinical translation and support the advancement of HAdV-D10 as a next-generation platform for gene delivery and vaccine development.
Funding Information
  • Medical Research Council (MR/N0137941/1)
  • Medical Research Council (MC_PC_17135)
  • Medical Research Council (MC_UU_00034/7)
  • Medical Research Council (MR/X011879/1)
  • Advanced Therapies Wales

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