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

Mundy, R. M.; Waraich, K.; Bates, E. A.; Rizkallah, P. J.; Baker, A. T.; Young, M. T.; Morris, E.; da Fonseca, P. C. A.; Bliss, C. M.; Matthews, D. A.; Bhella, D.; Parker, A. L.

doi:10.1101/2025.09.20.677498

bioRxiv · 10.1101/2025.09.20.677498

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

Mundy, R. M.·Waraich, K.·Bates, E. A.·Rizkallah, P. J.·Baker, A. T.·Young, M. T.·Morris, E.·da Fonseca, P. C. A.·Bliss, C. M.·Matthews, D. A.·Bhella, D.·Parker, A. L.

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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 [A], 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.

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Mundy, R. M., Waraich, K., Bates, E. A., Rizkallah, P. J., Baker, A. T., Young, M. T., Morris, E., da Fonseca, P. C. A., Bliss, C. M., Matthews, D. A., Bhella, D., Parker, A. L.. 2025-09-20. Identification of a novel structural motif and overexpression of key transcripts elucidated in Adenovirus 10. https://doi.org/10.1101/2025.09.20.677498

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