Valeria Lulla

Enteroviruses use two start sites to gain an edge 🦠🧬 #Enterovirus

Check out the latest @reviewcommons.org #preprintpeerreview of this study Lulla @valerialulla.bsky.social ‪ @cam.ac.uk

Reviews and author's reply here 👇
doi.org/10.1101/2025...

Many thanks to all authors from Lulla, Deane, Graham, Zilbauer and Firth labs! Great work from Rhian's PhD time👍
@campathology.bsky.social @atomicvirology.bsky.social @zilbauerlab.bsky.social

Flexibility and modulation of translation initiation in enterovirus genomes Enteroviruses comprise a large group of mammalian pathogens that often utilize two open reading frames (ORFs) to encode their proteins: the upstream protein (UP) and the main polyprotein. In some enteroviruses, in addition to the canonical upstream AUG (uAUG), there is another AUG that may represent an alternative upstream initiation site. An analysis of enterovirus sequences containing additional upstream AUGs identified several clusters, including strains of pathogenic Enterovirus alphacoxsackie and E. coxsackiepol. Using ribosome profiling on coxsackievirus CVA-13 (E. coxsackiepol), we demonstrate that both upstream AUG codons can be used for translation initiation in infected cells. Moreover, we confirm translation from both upstream AUGs using a reporter system. Mutating the additional upstream AUG in the context of CVA-13 did not result in phenotypic changes in immortalized cell lines. However, the wild-type virus outcompeted this mutant in human intestinal organoids and differentiated neuronal systems, representing an advantage in physiologically relevant infection sites. Mutation of the stop codon of the shorter upstream ORF led to dysregulated translation of the other ORFs in the reporter system, suggesting a potential role for the additional uORF in modulating the expression level of the other ORFs. These findings demonstrate the remarkable plasticity of enterovirus IRES-mediated initiation and the competitive advantage of double-upstream-AUG-containing viruses in terminally differentiated intestinal organoids and neuronal systems. ### Competing Interest Statement The authors have declared no competing interest.

📢Enteroviruses can have two upstream ORFs, and both can be translated! Led by Rhian O’Connor, this work shows the remarkable flexibility of enterovirus genomes and the advantage of double-uAUG virus in terminally differentiated cells – intestinal organoids and neurons
www.biorxiv.org/content/10.1...

Very proud of Dr Rhian O'Connor on smashing her PhD viva today! First one from the lab🥲 Thanks to great examiners Alex Borodavka and Julie Aspden - Rhian enjoyed it!🎉

We have found a capped flu RNA that was hiding in plain sight. In our preprint we show how this RNA activates RIG-I through a non-canonical mechanism. Fantastic work by Liza Elshina and many thanks to collaborators @alistairrussell.bsky.social and Joe Marcotrigiano! biorxiv.org/content/10.1...

I made a quick Starter Pack for scientists working on virus discovery - please reply if you’d like me to add you to the pack (or remove you) or to recommend anyone! #scisky go.bsky.app/HK1wxRb

Couldn’t find a virology starter pack so here’s one to get the ball rolling. Repost/reply if you are a virologist so I can find and add you to the list!

go.bsky.app/SinqoJU

Our lab is looking for a Research Assistant->
www.jobs.cam.ac.uk/job/44688/
Please share!

The astrovirus N-terminal nonstructural protein anchors replication complexes to the perinuclear ER ... bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution

Excited to share our first preprint of 2024!🎉
In astroviruses, the N-terminal domain of nonstructural protein drives the formation of replication complexes in tight association with perinuclear ER membranes. Great work by Hashim and colleagues!